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Sample records for induced hypertension pih

  1. [Results of placental flow measurements in patients with pregnancy-induced hypertension (PIH)].

    PubMed

    Voigt, R; Stoll, W; Estel, C

    1983-01-01

    On the basis of examination results in a total of 21 women with pregnancy-induced hypertension (PIH) the half-life of the inflow phase (as a reference parameter of nuclear medical placental flow measurement) and the birthweight were correlated with the findings in corresponding patients with complication-free pregnancies. The half-life was found to be significantly increased in cases of PIH, indicating a decrease in placental blood flow. The birthweight of newborns of women with PIH was statistically significantly lower than in the control group. The results obtained are discussed with reference to the literature. PMID:6682596

  2. Parameters of normotensive women and women with pregnancy induced hypertension (PIH) in Lusaka.

    PubMed

    Burgess, H A

    1991-09-01

    This paper reports results of a survey of mean arterial pressures (MAP) in a population of 125 control patients and 30 cases who developed pregnancy induced hypertension. The investigation was carried out to see if MAP would be a useful addition to methods used to screen for PIH. More of the cases had elevated MAP than did the controls, suggesting that use of this easily obtainable information may be helpful in identifying patients at risk for pregnancy--induced hypertension. Addition baseline information on the 155 patients and their pregnancy outcome is also presented. PMID:1797536

  3. A molecular variant of angiotensinogen (M235T) in Korean pregnancy-induced hypertension (PIH) patients

    SciTech Connect

    Kim, Y.T.; Lee, C.; Lim, H.K.

    1994-09-01

    Objective: to illustrate an association between Korean PIH patients and a molecular variant (M235T) in the angiotensinogen gene on chromosome 1q42-43. Material: DNA from peripheral blood of 21 Korean normo-tensive pregnant women and 16 Korean PIH patients. Methods: PCR was performed and the PCR product was digested with Tth111I. The amplification yielded a product of 165 bp. Presence of C at position 704 was identified by cleavage with Tth111I, that generated a fragment of 141 bp. Results: In the PIH group, 2 cases showed 141 bp, 5 cases showed 165 bp, and 9 cases showed both 165 and 141 bp. In the normo-tensive group, 4 cases showed 141 bp, 4 cases showed 165 bp, and 13 cases showed both bands. Conclusion: We could not provide any definite conclusion that the molecular variant (M235T) of angiotensinogen had an association with Korean PIH in this preliminary study. More cases are required to confirm the association between Korean PIH and the molecular variant (M235T) of angiotensinogen.

  4. Pregnancy-Induced Hypertension

    MedlinePLUS

    MENU Return to Web version Pregnancy-induced Hypertension Overview What is blood pressure? Blood pressure is the pressure in the blood vessels in ... The cause of PIH isn't known. Diagnosis & Tests What tests can show if I have PIH? ...

  5. [Management of pregnancy induced hypertension].

    PubMed

    Suzuki, Yoshikatsu; Matsuura, Ayano; Yamamoto, Tamao

    2015-11-01

    Pregnancy induced hypertension (PIH) is classified according to the severity of hypertension. The Japan Society of Hypertension made practice guidelines in 2014, and the Japan Society for the Study of Hypertension in Pregnancy made guidelines subsequently in 2015, too. Both guidelines state that the basic treatment for PIH is the interruption of pregnancy, and antihypertensive therapy should be given for protection in mother complicated by severe hypertension. The fetal heart rates should be monitored enough due to worsening fetal circulation. It recommends that methyldopa, hydralazine, labetalol, and long-acting nifedipine (only after 20 weeks of gestation) should be used as the first-choice antihypertensive oral drugs. Intravenous administration should be selected when a hypertensive emergency occurs. PMID:26619665

  6. Sodium transport inhibitors in pregnancy-induced hypertension.

    PubMed

    Poston, L

    1990-03-01

    In blacks and whites of similar socioeconomic background, the incidence of pregnancy-induced hypertension (PIH) is probably the same. In underdeveloped countries, however. PIH is often a life-threatening complication of pregnancy. Recent theories as to the etiology of PIH include the suggestion that vascular tone may be increased as a result of inhibition of active sodium transport in vascular smooth muscle. This may be the result of an inhibitor of sodium transport present in the serum. The literature concerning the demonstration of endogenous sodium transport inhibitors and endogenous digoxinlike immunoreactivity (EDLI) in PIH is reviewed and discussed. PMID:2176808

  7. Clinical significance of liver dysfunction in pregnancy-induced hypertension.

    PubMed

    Romero, R; Vizoso, J; Emamian, M; Duffy, T; Riely, C; Halford, T; Oyarzun, E; Naftolin, F; Hobbins, J C

    1988-04-01

    Hepatic dysfunction is one of the frequent manifestations of multisystemic involvement in preeclampsia. This study was conducted to establish the impact of liver dysfunction on maternal and neonatal outcome in women with pregnancy-induced hypertension (PIH). The prevalence of liver dysfunction as determined by an elevated serum glutamic oxalacetic transaminase (SGOT) concentration was 21% in a population of 355 patients with PIH. Liver dysfunction was associated with the presence of severe hypertension, proteinuria, a lower platelet count, and renal compromise (elevated blood urea nitrogen, creatinine, and uric acid serum concentrations). Abdominal pain was also associated with an SGOT elevation. Liver dysfunction was associated with intrauterine growth retardation and prematurity. Furthermore, the association with these neonatal complications was independent from the severity of the hypertension and the presence of proteinuria. Thus, we conclude that liver dysfunction is a frequent complication of PIH and that it is an independent risk factor for maternal and perinatal complications. PMID:3348861

  8. [Complication of ascites in pregnancy-induced hypertension].

    PubMed

    Cong, K J; Wang, T T

    1994-01-01

    Twenty three pregnancy-induced hypertension (PIH) patients with ascites were treated in Beijing Obstetrics and Gynecology Hospital from Jan. 1981 to April 1992. The incidence of ascites in PIH was 1.9/1000 in total in this study, and 21.6/1000 in severe PIH. Clinical manifestations showed an early onset of PIH at 29.4 +/- 4.8 weeks, and ascites occurred at 32.4 +/- 7.4 weeks. There were 18 cases out of 23 who had no routine antenatal care, all of them had complications with IUGR. Laboratory studies: ascites showed transudate in all of them except one with chronic nephritis exhibiting milky appearance. 10% of patients had abnormal complete blood count (CBC) and 13%-17% abnormal electrolytes. 17.0% of the patients had GPT > 30IU, 21.0% urea nitrogen > 35 g/L, 95.7% had plasma albumin < 35 g/L. The ratio of A/G was < 1.5 in all patients. We conclude that once PIH was 1.5 in all patients. We conclude that once PIH was complicated by ascites, it can not be cured by active treatment. It is an indication for termination of pregnancy. After delivery the ascites and pleural effusion gradually disappeared in 2 weeks. Perinatal mortality rate was as high as 42.1% because of premature induced labor and IUGR. PMID:8033624

  9. Calcium supplementation during pregnancy for reducing pregnancy induced hypertension.

    PubMed

    Cong, K; Chi, S; Liu, G

    1995-01-01

    Pregnancy induced hypertension (PIH) is a common complication in pregnancy and prenatal stage. Because the direct and indirect relationship between low calcium intake and many diseases, such as rachitis, young age myopia and hypertension, calcium supplementation has been a hot topic among nutritionists. Randomized trials of calcium supplementation during pregnancy were conducted in 212 healthy primipara. They were divided into 4 groups and gave 120mg, 240mg, 1g or 2g of calcium daily from 20 to 28 wks of gestation up to delivery respectively. As a result, the incidence of PIH was 8.9%, 7.5%, 8% and 4% respectively in these groups. The control group (106 pregnant women) who did not receive calcium gave an incidence of 18%. Supplementation of 2g of calcium daily showed significant results in lowering the incidence of PIH (P < 0.05) without any adverse effects. In 1992 calcium supplementation was widely used in antenatal-clinic. 200 cases with intake of 2g calcium were compared with corresponding non-calcium supplementation cases, and the incidence of PIH was 7.5% and 16.5% (P < 0.005) respectively. Mediating parathyroid hormone and renin activity are thought to be the effect of calcium on decreasing the incidence of PIH. PMID:7712843

  10. Higher cholesterol and insulin levels in pregnancy are associated with increased risk for pregnancy-induced hypertension.

    PubMed

    Solomon, C G; Carroll, J S; Okamura, K; Graves, S W; Seely, E W

    1999-03-01

    Hyperinsulinemia and dyslipidemia are known to be associated with essential hypertension but their role in pregnancy-induced hypertension remains unclear. We performed a case-control study comparing cholesterol, insulin, and glucose levels in the early third trimester of pregnancy among 31 women who developed pregnancy-induced hypertension (PIH) (either preeclampsia [n = 6] or nonproteinuric gestational hypertension [n = 25]), with 31 women remaining normotensive through pregnancy. As compared with women remaining normotensive, women subsequently developing PIH had higher fasting cholesterol levels (279 v 247 mg/dL; P = .02) and higher fasting insulin levels (13.3 v 7.9 microU/mL; P = .03), although fasting glucose levels and levels of glucose and insulin after glucose load did not differ significantly between groups. In comparing hypertensive subgroups, fasting insulin levels were significantly higher among women who subsequently developed preeclampsia, but not among those subsequently developing nonproteinuric gestational hypertension. Although women developing PIH had higher pregravid body mass index (25.1 v 22.6 kg/m2, P = .06), fasting cholesterol and insulin levels were associated with risk for PIH even after adjustment for body mass index and age (relative risks for one unit increase, respectively: 1.02 (P = .03) and 1.12 (P = .03). Higher fasting cholesterol and insulin levels in mid- to late pregnancy are associated with increased risk for PIH. These observations support a role for insulin resistance in the development of this complication of pregnancy. PMID:10192230

  11. Study of lipid profile, lipid peroxidation and vitamin E in pregnancy induced hypertension.

    PubMed

    Sahu, Suchanda; Abraham, Rebecca; Vedavalli, R; Daniel, Mary

    2009-01-01

    Pregnancy-induced hypertension (PIH) is a common medical complication of pregnancy with a high incidence. The study comprised of 30 normal and 30 PIH cases in their third trimester of pregnancy and the following estimations were done: Serum Malondialdehyde level (MDA), Vitamin E, triglycerides (TG), total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-C. The PIH cases had significant rise in both systolic and diastolic blood pressure (BP) (P=<0.0001). There was a significant rise in the fasting triglycerides, total cholesterol and LDL-C levels in PIH (P=<0.0001). MDA was twice in the cases and Vitamin E was half the levels that of controls (P=<0.0001). The level of rise of serum lipids did not significantly correlate with the rise or fall in MDA. In PIH cases there was a negative correlation of diastolic BP with MDA (P<0.05). Early detection of these parameters is going to aid in better management of PIH cases. PMID:20509330

  12. First trimester maternal blood rheology and pregnancy induced hypertension.

    PubMed

    Robins, J B; Woodward, M; Lowe, G; McCaul, P; Cheyne, H; Walker, J J

    2005-11-01

    This study evaluates the relationship between the first trimester assessment of maternal rheology and the subsequent development of pregnancy induced hypertension. This is a prospective observational study based in the Glasgow Royal Maternity Hospital, Scotland. From an original population of 744 consecutive antenatal attendees a total of 579 women were booked at less than 14 weeks' gestation. The main study group is a further subset comprising 251 primigravid women booking with a singleton pregnancy without essential hypertension. Previously published data from a group of non-pregnant women of similar age drawn from the same local community was used for external comparison. Blood samples were collected at the booking visit, from which fibrinogen, red cell aggregation, haematocrit and plasma, whole blood, relative and corrected viscosities were recorded. Information was obtained from the case notes in retrospect starting approximately 1 year after the first patients had first been recruited into the trial. The overall outcome of the pregnancies was noted with particular reference to pregnancy induced hypertension (PIH), birth weight, antepartum haemorrhage, pre-term labour, perinatal death, condition at delivery and neonatal complication. Our results show PIH is associated with a significantly raised mean blood viscosity and fibrinogen at time of booking. All significance disappears after adjustment for smoking, diastolic blood pressure and age. Viscosity is, however, only marginally non-significant (p = 0.07). In conclusion, blood rheology, in particular blood viscosity and fibrinogen, may play a predictive role in the development of pregnancy-induced hypertension. When combined with measurement of smoking and diastolic blood pressure at booking, these measurements could be used to calculate a risk score for the development of PIH, allowing targeting of antenatal care. Further data is required. PMID:16368576

  13. Parent-offspring conflict and the persistence of pregnancy-induced hypertension in modern humans.

    PubMed

    Hollegaard, Birgitte; Byars, Sean G; Lykke, Jacob; Boomsma, Jacobus J

    2013-01-01

    Preeclampsia is a major cause of perinatal mortality and disease affecting 5-10% of all pregnancies worldwide, but its etiology remains poorly understood despite considerable research effort. Parent-offspring conflict theory suggests that such hypertensive disorders of pregnancy may have evolved through the ability of fetal genes to increase maternal blood pressure as this enhances general nutrient supply. However, such mechanisms for inducing hypertension in pregnancy would need to incur sufficient offspring health benefits to compensate for the obvious risks for maternal and fetal health towards the end of pregnancy in order to explain why these disorders have not been removed by natural selection in our hunter-gatherer ancestors. We analyzed >750,000 live births in the Danish National Patient Registry and all registered medical diagnoses for up to 30 years after birth. We show that offspring exposed to pregnancy-induced hypertension (PIH) in trimester 1 had significantly reduced overall later-life disease risks, but increased risks when PIH exposure started or developed as preeclampsia in later trimesters. Similar patterns were found for first-year mortality. These results suggest that early PIH leading to improved postpartum survival and health represents a balanced compromise between the reproductive interests of parents and offspring, whereas later onset of PIH may reflect an unbalanced parent-offspring conflict at the detriment of maternal and offspring health. PMID:23451092

  14. Choroidal thickening and macular serous retinal detachment in pregnancy-induced hypertension

    PubMed Central

    Aoyagi, Ranko; Hayashi, Takaaki; Tsuneoka, Hiroshi

    2015-01-01

    Objective The purpose of this study was to report optical coherence tomography (OCT) and angiographic findings in a patient with pregnancy-induced hypertension (PIH). Case report A 39-year-old woman, who was diagnosed with PIH, reported blurred and distorted vision at 5 days after an emergency cesarean delivery. OCT revealed a large serous retinal detachment (SRD) that included areas in the macula, along with an increased choroidal thickness noted in both eyes. Indocyanine green angiograms indicated delayed filling of the choroidal circulation in the early phase but choroidal hyperpermeability in the mid-phase. The SRD was gradually resolving without any treatment except for antihypertensive drugs. At 40 days after the initial examination, OCT revealed both the disappearance of the SRD and marked improvement of the choroidal thickening. Conclusion Ophthalmologists need to be aware that PIH can cause choroidal ischemia, a breakdown of the outer blood–retinal barrier, and lead to the development of SRD. PMID:26635487

  15. Posterior Reversible Encephelopathy Syndrome Presenting as Quadriparesis in Pregnancy Induced Hypertension

    PubMed Central

    Pranita; Kumar, Ajit; Shahi, Seema

    2015-01-01

    Pregnancy Induced Hypertension (PIH) is a condition characterised by raised blood pressure in pregnancy. It affects approximately one out of every 14 pregnant women. Although PIH more commonly occurs during first pregnancy, it can also occur in subsequent pregnancies. It can present with variable complications related to vasospasm. But focal neurologic deficits are extremely rare in patients with PIH. We report a case of quadriparesis due to posterior reversible encephalopathy syndrome (PRES). A 36 year old full term pregnant female was admitted for emergency lower segment caesarean section (LSCS) as a result of uncontrolled PIH with early clinical signs of left ventricular failure. She was recovering well from pulmonary oedema after being provided with mechanical ventilation. However on 4th day she developed sudden onset quadriparesis without any alteration in sensorium, bladder & bowel disturbance or any sensory deficit. Diffusion weighted neuroimaging (DWI) was carried out which revealed finding suggestive of PRES. The patient was treated with antihypertensive which followed improvement in neurological deficit. Although rare, PRES should be considered as a potential cause of acute onset focal neurological deficit in pregnant females with PIH. With this case report we have tried to create awareness and vigilance about rare but potentially serious yet salvageable condition like PRES. PMID:26023585

  16. Maternal renal artery Doppler sonographic changes in pregnancy-induced hypertension in South West Nigeria

    PubMed Central

    Ogunmoroti, Olusanmi Abel; Ayoola, Oluwagbemiga Oluwole; Makinde, Olufemiwa Niyi; Idowu, Bukunmi Michael

    2015-01-01

    Background: To evaluate the renal arterial hemodynamic changes caused by pregnancy-induced hypertension using Doppler ultrasonography. Materials and Methods: Eighty (80) subjects with pregnancy-induced hypertension (PIH) and 160 controls (80 pregnant normotensive women and 80 healthy, non-pregnant women) underwent triplex renal sonography prospectively to determine their renal volumes and right renal artery Doppler indices. Results: The peak systolic velocity, end diastolic velocity, pulsatility index, systolic/diastolic ratio and acceleration time were respectively significantly higher in the PIH group (68.67 cm/s, 21.55 cm/s, 1.23, 3.38, 123.2 ms) than the pregnant, normotensive group (65.19 cm/s, 20.27 cm/s, 0.88, 3.35, 61.14 ms) and healthy, non-pregnant group (52.06 cm/s, 18.27 cm/s, 0.84, 2.90, 68.48 ms). Resistivity index was also increased in the PIH group, but this was not statistically significant. Conversely, the systolic acceleration was significantly lower in the PIH group (6.06 m/s2) compared to the pregnant, normotensive group (11.82 m/s2) and healthy, non-pregnant group (8.26 m/s2). The right renal volume of the PIH group (132.76 cm3) was significantly higher that of the pregnant, normotensive group (125.29 cm3) and healthy, non-pregnant group (91.66 cm3). The same pattern was observed in the left renal volume which was 168.78 cm3, 164.95 cm3 and 113.80 cm3 in the study groups, respectively. Conclusion: Renal Doppler ultrasound is clinically relevant in the diagnosis and follow-up of renal complications in patients with pregnancy-induced hypertension. PMID:26229227

  17. Is the serum l-arginine level during early pregnancy a predictor of pregnancy-induced hypertension?

    PubMed

    Wang, Jingwen; Kotani, Tomomi; Tsuda, Hiroyuki; Mano, Yukio; Sumigama, Seiji; Li, Hua; Komatsu, Koji; Miki, Rika; Maruta, Ei; Niwa, Yoshimitsu; Mitsui, Takashi; Yoshida, Shigeru; Yamashita, Mamoru; Tamakoshi, Koji; Kikkawa, Fumitaka

    2015-07-01

    The objective of this study was to determine the concentration of serum l-arginine in healthy pregnant women and infant cord blood and to compare them with those in patients with pregnancy-induced hypertension (PIH). The serum concentration of l-arginine in normal pregnant women at early gestation (n = 186) was determined and analyzed based on maternal factors such as the age, pre-pregnancy body mass index (BMI), smoking and alcohol habits before pregnancy. Similarly, the concentration of cord blood of the newborns (n = 142) was also analyzed. These values were compared with those in the PIH group (n = 21). The potential risk factors for PIH were also estimated. The serum concentration of l-arginine at early gestation in normal pregnant women (88.65 ± 19.96 µM) was not affected by the maternal age and BMI before pregnancy. A lower l-arginine concentration at early gestation (<70 µM) significantly elevated PIH risk [adjusted odds ratio (OR) = 4.26, 95% CI 1.29-14.50]. In addition, either women with large body mass before pregnancy (BMI>25 kg/m(2)) or primipara women also showed a significant association with PIH risk [adjusted OR = 10.55 (2.95-40.68); 5.25 (1.72-19.15), respectively]. In conclusion, a lower l-arginine concentration at early gestation, overweight before pregnancy (BMI>25 kg/m(2)) and primipara could predict to the development of PIH. PMID:26236104

  18. Platelet count in 100 cases of pregnancy induced hypertension.

    PubMed

    Rahim, R; Nahar, K; Khan, I A

    2010-01-01

    Hypertensive disorders are most common medical complication of pregnancy and the major causes of maternal & perinatal disease and death worldwide. The aim of the study was to see the platelet count in pregnancy induced hypertension (PIH). It was a prospective study. The study was done on 100 cases of PIH patients in Gynae & Obstetrics department of Mymensingh Medical College Hospital (MMCH) during the period of January to July 2006. Among the 100 cases 60 were eclamptic, 34 were pre eclamptic (PE) and 06 were gestational hypertensive (GH) patients. All the necessary informations and data were collected by interviewing the patients or their attendants on a pre-designed data collection sheet. Blood sample were collected from the patients and required investigations were done. Most of the eclampsia cases were from below average socioeconomic status of family, and other two groups were from average socioeconomic status of family. Among eclamptic patients 76.60% were primigravida. In eclamptic group 93.33% did not get any antenatal care but 83.33% GH cases had regular antenatal care. Among the eclamptic group mean maternal age was 23.12 years. In our study 47.00% had low platelet count (<1,50,000/cmm). Among eclampsia group 60.00% had low platelet count (<1,50,000/cmm). In our study 12% cases developed postpartum haemorrhage (PPH) and among them 66.67% had low platelet count (<1,50,000/cmm). Although there is chance of development of disseminated intravascular coagulation (DIC) and Liver Failure in patients with low platelet count, but in our study there is no such incidence. In our study mortality was 3% and all were in eclamptic group. Those patients had low platelet count 74.28% had low birth weight (LBW) babies. Platelet count is a very important investigation for antenatal mother having PIH, as it is directly related to maternal and perinatal outcome. PMID:20046164

  19. A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid, Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension

    PubMed Central

    Kemse, Nisha G.; Kale, Anvita A.; Joshi, Sadhana R.

    2014-01-01

    Objectives Our earlier studies have highlighted that an altered one carbon metabolism (vitamin B12, folic acid, and docosahexaenoic acid) is associated with preeclampsia. Preeclampsia is also known to be associated with oxidative stress and inflammation. The current study examines whether maternal folic acid, vitamin B12 and omega-3 fatty acid supplementation given either individually or in combination can ameliorate the oxidative stress markers in a rat model of pregnancy induced hypertension (PIH). Materials and Methods Pregnant Wistar rats were assigned to control and five treatment groups: PIH; PIH + vitamin B12; PIH + folic acid; PIH + Omega-3 fatty acids and PIH + combined micronutrient supplementation (vitamin B12 + folic acid + omega-3 fatty acids). L-Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day) was used to induce hypertension during pregnancy. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d20 of gestation. Results Animals from the PIH group demonstrated higher (p<0.01 for both) systolic and diastolic BP; lower (p<0.01) pup weight; higher dam plasma homocysteine (p<0.05) and dam and offspring malondialdehyde (MDA) (p<0.01), lower (p<0.05) placental and offspring liver DHA and higher (p<0.01) tumor necrosis factor–alpha (TNF–?) levels as compared to control. Individual micronutrient supplementation did not offer much benefit. In contrast, combined supplementation lowered systolic BP, homocysteine, MDA and placental TNF-? levels in dams and liver MDA and protein carbonyl in the offspring as compared to PIH group. Conclusion Key constituents of one carbon cycle (folic acid, vitamin B12 and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia. PMID:25405347

  20. Role of low dose aspirin in prevention of pregnancy induced hypertension.

    PubMed

    Tewari, S; Kaushish, R; Sharma, S; Gulati, N

    1997-02-01

    In a prospective randomised clinical study 50 primi or multigravidae with history of essential hypertension or pregnancy induced hypertension (PIH) in previous pregnancy were selected from antenatal clinics, on the basis of positive roll over test (ROT) carried out between 28 to 30 weeks of pregnancy. The study group comprised 25 women who received 50 mg aspirin daily from day of positive ROT till 37 weeks of pregnancy. Other 25 women served as control. The incidence of PIH in study and control group was 4% versus 28% and that of pre-term birth was 4% versus 24%. The mean birth weight of newborns in the two groups was 3.04 +/- 0.38 kg and 2.71 +/- 0.48 kg respectively. All these differences were statistically significant. No adverse maternal or neonatal complication due to aspirin was observed. PMID:9357241

  1. [Use of calcium for the prevention of pregnancy-induced hypertension].

    PubMed

    López-Jaramillo, P; de Félix, M

    1991-02-01

    The Andean population of Ecuador is exposed to major risk factors associated with pregnancy-induced hypertension (PIH). The disease is very frequent, and perinatal and maternal death rates are high. Recently a causal relationship has been suggested between dietary calcium deficiency and PIH, with the proposal that calcium supplements be given throughout pregnancy in order to prevent the disease. This article reviews a series of clinical tests carried out over a six-year period which have demonstrated that calcium supplementation is an effective low-cost measure for reducing the frequency of PIH in women whose intake of the mineral is low. It is not yet known how calcium reduces the risk of PIH. It is suggested that adequate intake of the mineral keeps serum levels of calcium within its narrow physiological limits; these are crucial for the synthesis of nitric oxide in the vascular endothelium, a substance that appears to be responsible for maintaining the vasodilatation that characterizes normal pregnancy. However, before the general use of calcium supplements can be recommended, it will be necessary to conduct epidemiological studies on larger numbers of women. PMID:1828158

  2. Nicotine Inhibits Cytokine Production by Placenta Cells via NF?B: Potential Role in Pregnancy-Induced Hypertension

    PubMed Central

    Dowling, Oonagh; Rochelson, Burton; Way, Kathleen; Al-Abed, Yousef; Metz, Christine N

    2007-01-01

    Pregnancy-induced hypertension (PIH), also known as preeclampsia, is one of the major causes of maternal and fetal death. While the precise cause of PIH is not known, aberrant cytokine production and placenta participation are considered to be important factors. Gestational cigarette smoking, which is widely accepted to be harmful to both the mother and fetus, is protective against PIH. Based on the antiinflammatory activity of nicotine, the major component of cigarettes, we examined the effect of nicotine and other cholinergic agonists on placental inflammatory responses ex vivo. We observed that nicotine and other cholinergic agonists significantly suppress placenta cytokine production following stimulation. Placenta cells express the ?7 nicotinic acetylcholine receptor (?7nAChR), and using cholinergic antagonists, we demonstrated that the antiinflammatory effect of nicotine and other cholinergic agonists is, in part, mediated through the nAChR pathway. By contrast, cholinergic stimulation had no effect on the expression of soluble fms-like tyrosine kinase (sFlt), an antiangiogenic substance implicated in maternal vascular dysfunction during PIH. Mechanistic studies reveal that cholinergic agonists exert their antiinflammatory effects through the NF?B pathway. Taken together, our results suggest that cholinergic agonists, including nicotine, may reduce cytokine production by placenta cells via NF?B to protect against PIH. PMID:17878927

  3. Early pregnancy maternal serum PAPP-A and urinary protein-creatinine ratio as predictive markers of pregnancy induced hypertension.

    PubMed

    Nasrin, B; Fatema, N; Jebunnessa, F; Shamim, S; Chowdhury, S B; Ali, L

    2010-04-01

    Pregnancy induced hypertension (PIH) is a major complication of pregnancy and is associated with high maternal and perinatal morbidity and mortality. The aim of this study was to investigate the possible causal association of PIH with maternal serum PAPP-A and urinary protein-creatinine ratio (UPCr) as well as to evaluate the usefulness of these two variables as predictive markers of PIH. A total 200 women of 8-16 weeks of pregnancy were enrolled in this study. All the patients were followed up till delivery for the development of pregnancy induced hypertension. Thirty patients were lost in the follow up, 3(1.76%) developed preeclampsia (PE) and 14(8.23%) gestational hypertension (GH). By a nested case-control design the 17 pregnancy induced hypertension cases were compared with 48 Controls with normal pregnancy outcome. Maternal serum PAPP-A was significantly lower in the pregnancy induced hypertension group compared to Control [mIU/ml, median (range) 1.8(0.70-4.1) vs. 5.45(2.7-10), p<0.001]. UPCr was significantly higher in the pregnancy induced hypertension group compared to Control (mg/mmol, mean+/-SD, 6.86+/-1.56 vs. 4.75+/-0.96, p<0.001). When tested as a predictive marker of pregnancy induced hypertension the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of maternal serum PAPP-A in the lowest 25th percentile were 82%, 95%, 87% and 93%. At 75th percentile the sensitivity, specificity, PPV and NPV of UPCr were 52%, 85%, 56% and 83% respectively. PMID:20395925

  4. The efficacy of biobehavioral and compliance interventions in the adjunctive treatment of mild pregnancy-induced hypertension.

    PubMed

    Somers, P J; Gevirtz, R N; Jasin, S E; Chin, H G

    1989-12-01

    This investigation assessed the efficacy of a biobehavioral intervention in the adjunctive treatment of mild pregnancy-induced hypertension (PIH), a potentially serious complication of pregnancy in which normotensive women develop hypertension, proteinuria, and edema of unknown etiology late in gestation. Forty-five women with symptoms of PIH were randomly assigned to one of three treatment conditions: bed rest alone (the most common obstetrical treatment), bed rest with individualized compliance enhancement training, or a four-session biobehavioral treatment consisting of bed rest, compliance enhancement training, and individualized thermal biofeedback-assisted relaxation training. Results indicated that while blood pressure for the bed rest and compliance enhancement groups continued to rise and pose an increasing health risk to maternal and fetal well-being, subjects in the biobehavioral group maintained their blood pressure at a significantly lower, and presumably safer, level. The biobehavioral treatment is hypothesized to affect blood pressure levels in subjects with mild PIH through the mediation of the sympathetic nervous system, decreasing peripheral vascular resistance and cardiac output. The results of this investigation suggest that the biobehavioral intervention may be an effective adjunct to bed rest in the treatment of mild PIH remote from term. PMID:2631971

  5. Pregnancy-induced hypertension and insulin resistance: evidence for a connection.

    PubMed

    Innes, K E; Wimsatt, J H

    1999-04-01

    PIH, the most common complication of pregnancy, remains a major source of maternal-child morbidity and mortality. Yet the etiology of this disorder is still little understood. There is now a growing body of evidence linking PIH and insulin resistance. Both proteinuric and non-proteinuric PIH predict future essential hypertension, and to a lesser extent, diabetes, disorders strongly related to glucose intolerance and insulin resistance. PIH is associated with diabetes, occurring in up to 50% of diabetic pregnancies. PIH is characterized by the same features that define IRS, including hypertension, dyslipidemia, disruption of endothelial and platelet function and related disturbances of prostanoid synthesis, coagulation and fibrinolytic abnormalities, hyperuricemia, atherosclerotic changes, and obesity. During the last decade, controlled studies by at least 11 different research groups in nine countries have established significant positive associations between both proteinuric and nonproteinuric PIH and various measures of insulin resistance. In particular, prospective investigations by at least five groups of investigators have indicated that relative hyperinsulinemia, glucose intolerance, and insulin insensitivity predict the subsequent development of PIH. These and other studies suggest that insulin resistance may play a causal role in the pathogenesis of PIH, and that some aspects of PIH may represent an early manifestation of IRS, precipitated by the profound metabolic and hemostatic challenges of gestation. PMID:10203292

  6. Brief review: hypertension in pregnancy : a manifestation of the insulin resistance syndrome?

    PubMed

    Solomon, C G; Seely, E W

    2001-02-01

    Pregnancy-induced hypertension (PIH), which includes both gestational hypertension and preeclampsia, is a common and morbid pregnancy complication for which the pathogenesis remains unclear. Emerging evidence suggests that insulin resistance, which has been linked to essential hypertension, may play a role in PIH. Conditions associated with increased insulin resistance, including gestational diabetes, polycystic ovary syndrome, and obesity, may predispose to hypertensive pregnancy. Furthermore, metabolic abnormalities linked to the insulin resistance syndrome are also observed in women with PIH to a greater degree than in normotensive pregnant women: These include glucose intolerance, hyperinsulinemia, hyperlipidemia, and high levels of plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-alpha. These observations suggest the possibility that insulin resistance may be involved in the pathogenesis of PIH and that approaches that improve insulin sensitivity might have benefit in the prevention or treatment of this syndrome, although this requires further study. PMID:11230277

  7. Validity in nulliparas of increased beta-human chorionic gonadotrophin at mid-term for predicting pregnancy-induced hypertension complicated with proteinuria and intrauterine growth retardation.

    PubMed

    Vaillant, P; David, E; Constant, I; Athmani, B; Devulder, G; Fievet, P; Gondry, J; Boulanger, J C; Fardelone, P; Fournier, A

    1996-01-01

    The objective of the present study was to investigate whether increased beta-human chorionic gonadotrophin (beta HCG) plasma concentrations in an unselected population of nulliparas could predict the occurrence of complicated pregnancy-induced hypertension (PIH). The design was that of a prospective population study. It was conducted at the obstetric departments of Amiens University Hospital and Creil General Hospital on 434 consecutive nulliparas with singleton pregnancies after natural fertilization who accepted the systematic offer of trisomy 21 screening but for whom this disorder was finally estimated. Measurement of plasma concentration of beta HCG (ELISA method) was carried out between 14 and 20 weeks (mean: 17 weeks) of amenorrhea, and measurement of blood pressure and proteinuria (> 300 mg/24 h or Albustix +2) during the first, second and third term and 2-3 months after the delivery, as well as measurement of birth weight for determination of small for gestational age (SGA) babies, 37 women developed PIH, 10 without other complication, 16 with proteinuria (5 of which with SGA babies) and 11 with SGA babies. Furthermore 2 patients presented abruptio placentae without PIH. 395 women did not develop PIH including 389 normotensive women and 6 chronic hypertensive patients without superimposed toxemia. Only 1 was diabetic. None had chronic renal disease. Mean (+/- SD) levels of beta HCG were higher in PIH than in controls: 46,805 +/- 19,068 versus 23,479 +/- 13,463 IU. A pathologic threshold was chosen as the mean for the whole population + 1 SD: 25,613 + 15,479 = 41,082 IU. Elevated levels (above this value) were significantly associated with isolated PIH or PIH complicated with proteinuria and/or with SGA babies. The positive predictive value of this criterion was respectively 11, 15 and 12% for each of these complications. The relative risk (and 95% confidence limit) of women with elevated beta HCG for each of these complications was 20 (6-79), 11 (4-43) and 22 (7-93). Elevated plasma beta HCG found around 17 weeks of amenorrhea predicts PIH complicated with either proteinuria or SGA babies with a positive predictive value comparable to that of the best and earliest test proposed up to now to select nulliparas at high risk of preeclampsia, namely the abnormalities of the Doppler waveforms of the uterine arteries. Since this test is simpler to perform, it represents the most convenient method to screen a population of nulliparas for evaluation of the benefits of low-dose aspirin. PMID:8730421

  8. Hypertension during pregnancy in insulin-dependent diabetic women.

    PubMed

    Siddiqi, T; Rosenn, B; Mimouni, F; Khoury, J; Miodovnik, M

    1991-04-01

    Insulin-dependent diabetic patients are at increased risk for hypertensive disorders of pregnancy. This study was designed to study prospectively the rate of pregnancy-induced hypertension (PIH) in 175 insulin-dependent diabetic pregnancies (88 White classes B-C, 87 classes D-RT). Pregnancy-induced hypertension was defined as two or more occurrences after 20 weeks' gestation of a mean arterial pressure (MAP) of 105 mmHg or greater or an increase of 20 mmHg or greater from the baseline MAP. The rate of PIH in the diabetic population was 15.4% and was significantly associated with nulliparity, poor glycemic control in the first and second trimesters, and advanced White class. Neonatal outcome was not significantly altered in the presence of PIH. We speculate that improved glycemic control throughout pregnancy might reduce the rate of this complication in diabetic patients. PMID:2002972

  9. Drug induced hypertension--An unappreciated cause of secondary hypertension.

    PubMed

    Grossman, Alon; Messerli, Franz H; Grossman, Ehud

    2015-09-15

    Most patients with hypertension have essential hypertension or well-known forms of secondary hypertension, such as renal disease, renal artery stenosis, or common endocrine diseases (hyperaldosteronism or pheochromocytoma). Physicians are less aware of drug induced hypertension. A variety of therapeutic agents or chemical substances may increase blood pressure. When a patient with well controlled hypertension is presented with acute blood pressure elevation, use of drug or chemical substance which increases blood pressure should be suspected. Drug-induced blood pressure increases are usually minor and short-lived, although rare hypertensive emergencies associated with use of certain drugs have been reported. Careful evaluation of prescription and non-prescription medications is crucial in the evaluation of the hypertensive individual and may obviate the need for expensive and unnecessary evaluations. Discontinuation of the offending agent will usually achieve adequate blood pressure control. When use of a chemical agent which increases blood pressure is mandatory, anti-hypertensive therapy may facilitate continued use of this agent. We summarize the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. PMID:26096556

  10. Application of Optical Coherence Tomography and Contrast Sensitivity Test for Observing Fundus Changes of Patients With Pregnancy-Induced Hypertension Syndrome.

    PubMed

    Wang, Zhixue; Zou, Yuanyuan; Li, Wenying; Wang, Xueyan; Zhang, Min; Wang, Wenying

    2015-11-01

    This study was aimed to investigate the fundus changes of patients with pregnancy-induced hypertension syndrome (PIHS) using optical coherence tomography (OCT) technology and contrast sensitivity (CS) tests.Ninety-eight patients with PIHS underwent routine eye examinations including vision correction, fundus examination, OCT, and CS tests. The CS test was performed at low, medium, and high frequency, respectively. Moreover, the difference in CS tests between 2 groups was analyzed by independent-samples T test. The Kruskal-Wallis rank sum test and linear regression model were used to detect the correlation of OCT with CS, respectively. Meanwhile Satterthwaite approximate T test was adopted for pairwise comparisons after nonparametric analysis of variance.The OCT test revealed that 56.76% of the examined eyes showed shallow retinal detachment in the macula lutea and around the optic disk. The differences in CS at each spatial frequency between the case and control group were statistically significant (P?PIHS. OCT and CS tests might be valuable methods in observing fundus changes for PIHS patients. PMID:26554764

  11. Transient blindness in pregnancy induced hypertension.

    PubMed

    Nalliah, S; Thavarashah, A S

    1989-07-01

    Transient blindness associated with pregnancy induced hypertension without neurological symptoms is a rare phenomenon. The blindness in these cases is postulated to be of "cortical blindness". Two such cases occurring immediately after childbirth are presented. The ophthalmic manifestations of this complication of pregnancy induced hypertension and the importance of an urgent evaluation are discussed. PMID:2569423

  12. [Anesthetic Management of a Parturient with Eclampsia, Posterior Reversible Encephalopathy Syndrome and Pulmonary Edema due to Pregnancy-induced Hypertension].

    PubMed

    Aida, Junko; Okutani, Hiroai; Oda, Yutaka; Okutani, Ryu

    2015-08-01

    A 27-year-old woman with mental retardation was admitted to a nearby hospital for an abrupt onset of seizure. Physical examination revealed remarkable hypertension and pregnancy with estimated gestational age of 28th week. Severe pulmonary edema and hypoxia led to a diagnosis of pregnancy-induced hypertension (PIH) accompanied by eclampsia. She was orotracheally intubated because of refractory seizure and hypoxemia, and transferred to our hospital for further treatment. Besides severe hypoxia and hypercapnea, an enhanced lesion was detected in the left posterior cerebrum by brain MRI. No abnormal findings were detected in the fetus, with heart rate of 150 beats x min. She was diagnosed with posterior reversible encephalopathy syndrome (PRES) caused by PIH and emergency cesarean section under general anesthesia was scheduled. A male newborn was delivered with Apgar score of 1/4 (1/5 min), followed by starting continuous infusion of nicardipine for controlling hypertension. Chest X-P on completion of surgery revealed remarkably alleviated pulmonary edema. She received intensive treatment and continued positive pressure ventilation for four days after delivery. She recovered with no neurological deficits and her child was well without any complications. PMID:26442424

  13. Drug-induced hypertension: an unappreciated cause of secondary hypertension.

    PubMed

    Grossman, Ehud; Messerli, Franz H

    2012-01-01

    A myriad variety of therapeutic agents or chemical substances can induce either a transient or persistent increase in blood pressure, or interfere with the blood pressure-lowering effects of antihypertensive drugs. Some agents cause either sodium retention or extracellular volume expansion, or activate directly or indirectly the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower blood pressure may paradoxically increase blood pressure, or an increase in pressure may be encountered after their discontinuation. In general, drug-induced pressure increases are small and transient: however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure have been reported. The deleterious effect of therapeutic agents is more pronounced in patients with preexisting hypertension, in those with renal failure, and in the elderly. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and obviate unnecessary evaluation and facilitate antihypertensive therapy. Once chemical-induced hypertension has been identified, discontinuation of the causative agent is recommended, although hypertension can often be managed by specific therapy and dose adjustment if continued use of the offending agent is mandatory. The present review summarizes the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. PMID:22195528

  14. Quantitative peptidomic analysis by a newly developed one-step direct transfer technology without depletion of major blood proteins: its potential utility for monitoring of pathophysiological status in pregnancy-induced hypertension.

    PubMed

    Araki, Yoshihiko; Nonaka, Daisuke; Tajima, Atsushi; Maruyama, Mayuko; Nitto, Takeaki; Ishikawa, Hitoshi; Yoshitake, Hiroshi; Yoshida, Emiko; Kuronaka, Noriko; Asada, Kyoichi; Yanagida, Mitsuaki; Nojima, Michio; Yoshida, Koyo; Takamori, Kenji; Hashiguchi, Teruto; Maruyama, Ikuro; Lee, Lyang-Ja; Tanaka, Kenji

    2011-07-01

    We have recently developed a new target plate (BLOTCHIP®) for MALDI-MS. An advantage of this procedure is that it does not require the lowering of protein concentrations in test samples prior to analysis. Accordingly, this new technology enables the detection of peptides present in blood samples, including those that would otherwise be adsorbed to abundant blood proteins and would thus escape detection. Using this technology, we analyzed the peripheral blood of patients with pregnancy-induced hypertension (PIH; the most common serious complication of pregnancy) to test a potential utility of the technology for monitoring of the pathophysiological status. In the present study, we found 23 characteristic peptides for PIH in the blood serum of pregnant women. Offline LC-MALDI MS/MS identified 7 of the 23 peptides as fragments derived from kininogen-1 (three peptides), fibrinogen-?, complement component C4-A/B, ?-2-HS-glycoprotein and inter-?-trypsin inhibitor heavy chain H4. 2-D scatter plots with combinations of the peptides found in the present study can be grouped for pregnant women with/without PIH, which would be satisfactory reflected for their status. Additionally, the levels of most of these peptides found were significantly decreased by albumin/IgG depletion prior to BLOTCHIP® analysis in accordance with conventional proteomics procedures. These results indicated that BLOTCHIP® analysis can be applied for discovery study of PIH biomarker candidates. PMID:21630454

  15. [Iatrogenic and drug-induced hypertension].

    PubMed

    Mounier-Vehier, Claire; Boudghène, Fanny; Claisse, Gonzague; Delsart, Pascal

    2015-06-01

    Various toxic or drug agents can induce arterial hypertension, aggravate or limit the efficiency of anti-hypertensive drugs. Iatrogenic and drug-induced hypertension should be well known by the clinicians and the pharmacists, given the impact for driving the management of patients. In the food, an excessive alcohol consumption (more than 30 g per day) and more rarely glycerizine (active ingredient of the licorice) should be systematically looked for in front of a recent hypertension or do not respond to usual treatment. In the list of offending medicines, we must remember ethinyl estradiol contained in the contraception (oral, vaginal ring or transcutaneous patch), non steroidal anti-inflammatory drugs, immunosuppressants (cyclosporine, tacrolimus), vascular endothelial growth factor and its receptor R2 (avastin, inhibitors of receptor tyrosine kinases), recombinant human erythropoietin, sympathomimetics (nasal decongestants), anabolic steroids, bromocriptine (inhibitor of lactation), psychotropes (tricyclics antidepressants, monoamine oxydase inhibitors). The diagnosis of iatrogenic hypertensions should be systematically suspected in front of a suggestive clinical context with a meticulous food questioning because these hypertensions are partially or fully reversible after exposure stops. PMID:26298906

  16. Impact of Computer-Based Pregnancy-Induced Hypertension and Diabetes Decision Aids on Empowering Pregnant Women

    PubMed Central

    Aslani, Azam; Tara, Fatemeh; Ghalighi, Lila; Pournik, Omid; Ensing, Sabine; Abu-Hanna, Ameen

    2014-01-01

    Objectives We designed a computer-based decision aid (CDA) for use by pregnant women at home to investigate and participate in solving their pregnancy problems related to pregnancy-induced hypertension (PIH) and gestational diabetes (GD). The system cannot and is not intended to replace visits to physicians; rather it can help women focus on the most important symptoms and provides guidance on when to see a doctor. Methods The study is a randomized controlled trial, which is performed among Iranian pregnant women. For subjects, 420 healthy pregnant women have been recruited from two private and two public prenatal centers. The intervention group will receive the CDA for use at home, and the control group will receive care as usual. The CDA relies on knowledge extracted from the national guidelines on PIH and GD. Results The two primary outcomes for the study are self-efficacy and knowledge. Self-efficacy will be measured by the Stanford self-efficacy scale and knowledge will be evaluated by 15 binary (true/false) questions provided by the researchers. Secondary outcomes include type and frequency of doctor and/or medical center visits; blood pressure and blood sugar changes based on the national guidelines and according to pregnancy records, and anxiety will be assessed by the state component of the short Spielberger anxiety scale. Conclusions This paper describes the design of a CDA and a protocol for a randomized controlled trial to study the effects of the CDA on self-efficacy and knowledge of pregnant women pertaining to PIH and GD. Differences in the primary outcomes will be analyzed using 'intention-to-treat' principles. PMID:25405062

  17. Fish Oil Supplementation does not Reduce Risks of Gestational Diabetes Mellitus, Pregnancy-Induced Hypertension, or Pre-Eclampsia: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Chen, Bing; Ji, Xinran; Zhang, Lei; Hou, Zhaohui; Li, Chundong; Tong, Ying

    2015-01-01

    Background The effects of gestational supplementation with fish oil on risks for gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and pre-eclampsia (PE) have not been confirmed. In this study, a meta-analysis was performed to evaluate the effect of fish oil supplementation on these gestational complications. Material/Methods Randomized controlled human trials that investigated the effects of fish oil supplementation in pregnant women were identified by a systematic search of Medline, Embase, and Cochrane’s Library, and references of related reviews and studies up to December 2014. Relative risks (RRs) for GDM, PIH, and PE were the outcomes of interest. Fixed-effects or random-effects models were applied according to the heterogeneity. Results Thirteen comparisons from 11 published articles, including more than 5000 participants, were included. The results showed that fish oil supplementation was not associated with reduced risks for GDM (RR=1.06, 95% confidence interval [CI]: 0.85–1.32, p=0.60), PIH (RR=1.03, 95% CI: 0.89–1.20, p=0.66), or PE (RR=0.93, 95% CI: 0.74–1.16, p=0.51). No statistically significant heterogeneity was detected for the comparison of each outcome. The effects of fish oil on these gestational complications were consistent between women with low-risk and high-risk pregnancies. Conclusions Gestational supplementation with fish oil during the second or third trimester of pregnancy is not associated with reduced risks for GDM, PIH, or PE. Other possible benefits of fish oil supplementation during pregnancy warrant further evaluation. PMID:26256041

  18. Hypertension induced by liquorice tea.

    PubMed

    Allcock, Emily; Cowdery, James

    2015-01-01

    A 45-year-old woman presented to her general practitioner with a 4-month history of hot flushes, sweating and headaches. On examination, she was found to be hypertensive, and blood tests revealed mild hypokalaemia. While awaiting the results of further investigation into the cause of her elevated blood pressure, the patient conducted her own research and identified liquorice tea as the potential cause of her symptoms. The patient had been drinking up to six cups of liquorice tea per day as a substitute for caffeinated tea and fruit-based infusions. The patient immediately stopped consuming the drink and within 2 weeks her symptoms, hypertension and hypokalaemia had entirely resolved. PMID:26077805

  19. [Liquorice-induced hypertension and hypokalaemia].

    PubMed

    Nielsen, Mette Lundgren; Pareek, Manan; Andersen, Inger

    2012-04-01

    Consumption of large amounts of liquorice can cause hypertension and hypokalaemia. Liquorice contains glycyrrhetinic acid, which inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase type 2, and ultimately leads to an apparent mineralocorticoid excess syndrome. This case report describes a 50 year-old woman presenting with hypertension and hypokalaemia-induced limb paresis due to chronic liquorice ingestion. The patient was treated with potassium supplementation and spironolactone. Her blood pressure and electrolyte status normalised within a month after cessation of liquorice intake. PMID:22487411

  20. A Study on Atherogenic Indices of Pregnancy Induced Hypertension Patients as Compared to Normal Pregnant Women

    PubMed Central

    Pathak, Mauchumi Saikia; Paul, Anindita

    2015-01-01

    Introduction Pregnancy induced hypertension (PIH) includes Gestational hypertension, Pre-eclampsia and Eclampsia and is one of the most common obstetric complication. Worldwide about 76,000 pregnant women die each year from pre-eclampsia and related hypertensive disorders. The aetiology of Pre-eclampsia is unknown but it is thought to be related to abnormal development of placenta. Several studies have shown the presence of reduced endothelial function in pre-eclamptic pregnancy. Endothelial dysfunction is also a feature of atherosclerosis. Aim To assess fasting lipid profile and atherogenic indices in women diagnosed with pre-eclampsia as well as in women with normal pregnancy and to correlate the findings of pre-eclamptic women with that of normal pregnant women, in an attempt to utilize the data for the development of a new clinical approach for early recognition and prevention of risk of future cardiovascular diseases in women with PIH. Materials and Methods This case-control study was conducted on 50 pre-eclampsia patients who were in third trimester of pregnancy (Case group). A control group of 50 age and gestational age matched normal pregnant women was taken. Strict inclusion and exclusion criteria were followed. Fasting Lipid profile parameters were assessed and used to calculate the atherogenic indices namely Atherogenic index of plasma (AIP), Cardiac risk ratio (CRR) and Atherogenic coefficient (AC). Statistical Analysis was done by using student’s t-test. Mann-Whitney U-test was used wherever applicable and correlations between the variables were estimated by Pearson’s correlation coefficients. Results There was an extremely significant (p<0.0001) increase in Atherogenic indices (AIP, CRR and AC) in case group as compared to the control group. A positive and significant correlation of systolic blood pressure with AIP (r=0.3583), CRR (r=0.3137), AC (r=0.3193) was found in cases. There was a positive and significant correlation between gestational age and atherogenic indices in the case group. Conclusion Women with pre-eclampsia present abnormalities in lipid profile and these lipids turn out to be a risk factor for cardiovascular complications. Evaluation of the atherogenic indices during pregnancy may help prevent this risk. PMID:26393117

  1. Complication of insulin-dependent diabetic pregnancies by preeclampsia and/or chronic hypertension: analysis of outcome.

    PubMed

    Diamond, M P; Shah, D M; Hester, R A; Vaughn, W K; Cotton, R B; Boehm, F H

    1985-10-01

    The significance of hypertensive complications of insulin-dependent diabetic pregnancies (IDDP) has not been well examined since the early reports of Pedersen, which demonstrated an increased risk of neonatal death in women with pregnancy induced hypertension (PIH). To assess the effect of both PIH and chronic hypertension (CH) on outcome of IDDP managed using contemporary obstetrical and diabetic management, we reviewed the records of all 199 IDDP delivered at our institution over a 7-year period. Patients were classified as having PIH (Group 1, n = 37), CH (Group 2, n = 18) or both (Group 3, n = 4) on the basis of standard clinical criteria. All other IDDP were placed in the control group (Group 4, n = 140). Comparing all groups, significant differences were found for maternal age (P less than .0001) and distribution among White's Classes (P less than .0001). There was no significant difference in estimated gestational age (EGA) at delivery, birthweight, Apgar scores, hypoglycemia, hyperbilirubinemia, or congenital anomalies. Intrauterine fetal death (IUFD) was no more common in Groups 1, 2 or 3 than in Group 4; however, IDDP with CH were significantly more likely to have had previous stillbirths than IDDP with PIH (P = .011) or control IDDP (P = .017). Contrary to common clinical belief, the "stress" of CH and PIH did not offer protection to the newborn in the development of RDS or HMD. In fact, Group 3 infants had a higher rate of HMD than control infants (P = .024).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4052175

  2. Sildenafil attenuates placental ischemia-induced hypertension.

    PubMed

    George, Eric M; Palei, Ana C; Dent, Edward A; Granger, Joey P

    2013-08-15

    Preeclampsia is a complication of pregnancy that is marked by hypertension, proteinuria, and maternal endothelial dysfunction. A central factor in the etiology of the disease is the development of placental hypoxia/ischemia, which releases pathogenic soluble factors. There is currently no effective treatment for preeclampsia, but the phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been suggested, as PDE-5 is enriched in the uterus, and its antagonism could improve uteroplacental function. Here, we report in the reduced uterine perfusion pressure (RUPP) rat model that administration of oral sildenafil is effective in attenuating placental ischemia-induced hypertension during gestation. RUPP animals have significantly elevated arterial pressure compared with control animals (132 ± 3 vs. 100 ± 2 mmHg; P < 0.05). Administration of oral sildenafil (45 mg·kg?¹·day?¹) had no effect on blood pressure in control rats but decreased pressure in RUPP rats (115 ± 1 mmHg; P < 0.05). RUPP induced changes in placental sFlt-1, and vascular endothelial growth factor (VEGF) was unaffected by sildenafil administration, as was the decrease in free plasma VEGF. RUPP animals had a significant increase in medullary PDE-5/?-actin ratio (1 ± 0.14 vs. 1.63 ± 0.18; P < 0.05) expression with a resulting reduction in renal medullary cGMP (1.5 ± 0.15 vs. 0.99 ± 0.1 pmol/?g protein, P < 0.05) compared with controls. Although sildenafil had no effect on renal medullary cGMP in control animals, it significantly increased cGMP in RUPP animals (1.3 ± 0.1 pmol/?g protein; P < 0.05). These data suggest that sildenafil might provide an effective therapeutic option for the management of hypertension during preeclampsia. PMID:23785075

  3. New developments in the pathogenesis of obesity-induced hypertension.

    PubMed

    Kotsis, Vasilios; Nilsson, Peter; Grassi, Guido; Mancia, Giuseppe; Redon, Josep; Luft, Frank; Schmieder, Roland; Engeli, Stefan; Stabouli, Stella; Antza, Christina; Pall, Denes; Schlaich, Markus; Jordan, Jens

    2015-08-01

    Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of ?-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity. PMID:26103132

  4. Assessment of Nephroprotective Potential of Histochrome during Induced Arterial Hypertension.

    PubMed

    Agafonova, I G; Bogdanovich, R N; Kolosova, N G

    2015-12-01

    Magnetic resonance tomography was employed to verify endothelial dysfunction of renal arteries in Wistar and OXYS rats under conditions of induced arterial hypertension. Angiography revealed changes in the size and form of renal arteries of hypertensive animals. In hypertensive rats, histochrome exerted a benevolent therapeutic effect in renal arteries: it decreased BP, diminished thrombus formation in fi ne capillaries and arterioles, demonstrated the anticoagulant properties, partially improved endothelial dysfunction of small renal arteries, and up-regulated the glomerular filtration. PMID:26645289

  5. Radiation induced heart disease in hypertensive rats

    SciTech Connect

    Lauk, S.; Trott, K.R.

    1988-01-01

    Spontaneously hypertensive Wistar rats were given single doses of X rays to their heart. Irradiation decreased the blood pressure before any myocardial radiation damage was apparent. Male rats, which were more hypertensive than female rats, had a shorter survival time after local heart irradiation than female rats. Antihypertensive treatment with hydralazine did not increase the survival time. It is considered that myocardial hypertrophy is the cause of the increased susceptibility of spontaneously hypertensive rats to local heart irradiation.

  6. Spaceflight-Induced Intracranial Hypertension: An Overview

    NASA Technical Reports Server (NTRS)

    Traver, William J.

    2011-01-01

    This slide presentation is an overview of the some of the known results of spaceflight induced intracranial hypertension. Historical information from Gemini 5, Apollo, and the space shuttle programs indicated that some vision impairment was reported and a comparison between these historical missions and present missions is included. Optic Disc Edema, Globe Flattening, Choroidal Folds, Hyperopic Shifts and Raised Intracranial Pressure has occurred in Astronauts During and After Long Duration Space Flight. Views illustrate the occurrence of Optic Disc Edema, Globe Flattening, and Choroidal Folds. There are views of the Arachnoid Granulations and Venous return, and the question of spinal or venous compliance issues is discussed. The question of increased blood flow and its relation to increased Cerebrospinal fluid (CSF) is raised. Most observed on-orbit papilledema does not progress, and this might be a function of plateau homeostasis for the higher level of intracranial pressure. There are seven cases of astronauts experiencing in flight and post flight symptoms, which are summarized and follow-up is reviewed along with a comparison of the treatment options. The question is "is there other involvement besides vision," and other Clinical implications are raised,

  7. Angiotensin type 1 receptor blockade prevents cardiac remodeling in mice with pregnancy-associated hypertension.

    PubMed

    Sakairi, Akira; Ishida, Junji; Honjo, Kaori; Inaba, Saki; Nakamura, Shoko; Sugiyama, Fumihiro; Yagami, Ken-Ichi; Fukamizu, Akiyoshi

    2008-12-01

    Pregnancy-induced hypertension (PIH) is a life-threatening disorder for both mother and fetus; cardiac dysfunction is the major complication and can result in further deterioration. Recently, it has been recognized that aberrant activation of angiotensin type 1 receptor (AT1) signaling contributes to the pathogenesis of PIH, but the details of the relationship between cardiac injury and enhanced AT1 signaling in PIH are still unclear. We previously generated a transgenic mouse model of pregnancy-associated hypertension (PAH) via overproduction of angiotensin II, an endogenous ligand of AT1, in the maternal circulation during late pregnancy. In the present study, we administered olmesartan, an AT1 blocker, to suppress redundant AT1 signaling in PAH mice and evaluated the efficacy of this treatment in cardiac remodeling. Olmesartan treatment significantly lowered the blood pressure of PAH mice, and hypertrophy as well as increased plasma levels of cardiac injury markers were also markedly reduced. Histological analyses revealed that morphological abnormalities and fibrosis in the hearts of PAH mice recovered to the levels of normal pregnant wild-type mice after the administration of olmesartan. Moreover, in fibrotic regions of PAH hearts, olmesartan treatment significantly decreased the extent of cardiac injury and apoptosis. These results indicate that the activation of AT1 signaling pathways during maternal hypertension plays a critical role in cardiac remodeling in PAH mice, and suggest that treatment with an AT1 blocker could effectively ameliorate cardiac dysfunction during pregnancy with hypertension in vivo. PMID:19139606

  8. [Blood pressure variability-induced aggravation of hypertensive organ damages].

    PubMed

    Kai, Hisashi

    2015-11-01

    There is increasing evidence that not only the elevation of systolic and diastolic blood pressure(BP) but also the increase in BP variability (or fluctuation) are associated with hypertensive organ damages and the morbidity and mortality of cerebrovascular and cardiovascular events, as well as cognitive dysfunction. However, the molecular mechanism whereby the increase in BP variability aggravates hypertensive organ damages remains unknown. Thus, we created a rat chronic model of a combination of hypertension and large BP variability by performing bilateral sino-aortic denervation in spontaneously hypertensive rat. A series of our studies using this model revealed that large BP variability induces chronic myocardial inflammation by activating local angiotensin II and mineralocorticoid receptor systems and thereby aggravates cardiac hypertrophy and myocardial fibrosis, leading to systolic dysfunction, in hypertensive hearts. In addition, large BP variability induces the aggravation of arteriolosclerotic changes and ischemic cortical fibrosis in hypertensive kidney via local angiotensin II system. It is interesting that the initial target sites of the large BP variability are the intramyocardial arterioles in the heart and pre-glomerular arterioles in the juxtamedullary renal cortex, so called "strain vessels". Accordingly, we advocate new concept that the large BP-induced aggravation of hypertensive organ damage is attributable to "strain vessel vasculopathy". PMID:26619672

  9. Human PIH1 associates with histone H4 to mediate the glucose-dependent enhancement of pre-rRNA synthesis.

    PubMed

    Zhai, Niu; Zhao, Zhong-liang; Cheng, Mo-bin; Di, Yu-wei; Yan, Hai-xia; Cao, Chun-yu; Dai, Hui; Zhang, Ye; Shen, Yu-fei

    2012-08-01

    Ribosome biogenesis is critical in the growth of eukaryotic cells, in which the synthesis of precursor ribosomal RNA is the first and rate-limiting step. Here, we show that human PIH1 domain-containing protein 1 (PIH1) interacts directly with histone H4 and recruits the Brg1-SWI/SNF complex via SNF5 to human rRNA genes. This process is likely involved in PIH1-dependent DNase I-hypersensitive chromatin remodeling at the core promoter of the rRNA genes. PIH1 mediates the occupancy of not only the Brg1 complex but also the Pol I complex at the core promoter and enhances transcription initiation of rRNA genes. Additionally, the interaction between PIH1 and H4K16 expels TIP5, a component of the silencing nucleolar remodeling complex (NoRC), from the core region, suggesting that PIH1 is involved in the derepression of NoRC-silenced rRNA genes. These data indicate that PIH1 is a positive regulator of human rRNA genes and is of great importance for the recovery of human cells from nutrient starvation and the transition to glucose-induced exponential growth in vivo. PMID:22368283

  10. Mechanisms underlying the hypertensive response induced by capsaicin.

    PubMed

    Dutta, Abhaya; Deshpande, Shripad B

    2010-11-19

    Acute ingestion of large quantity of chili peppers (rich source of capsaicin) produced hypertensive crisis in a patient. The hypertensive response was explained on the basis of decreased vasodilator substance calcitonin gene-related peptide (CGRP) from sensory nerve terminals by capsaicin. Here we present our experimental observations in anaesthetized rats regarding the mechanisms underlying hypertensive response induced by capsaicin. Our results demonstrate non-involvement of adrenergic and angiotensinergic mechanisms and also the cardiac changes in producing the response. Thus, the direct action of capsaicin on vascular smooth muscle or the activation of endothelin is proposed. PMID:20223533

  11. Maternal serum ischemia modified albumin as a marker for hypertensive disorders of pregnancy: a pilot study

    PubMed Central

    Vyakaranam, Sapna; Bhongir, Aparna Varma; Patlolla, Dakshayani; Chintapally, Rekha

    2015-01-01

    Background Hypoxia driven oxidative stress of the placenta contributes to the pathogenesis of preeclampsia. Serum Ischemia Modified Albumin (IMA) has recently emerged as an oxidative stress marker, used in diagnosis of cardiac ischemia. Aim: To determine the efficiency of serum IMA in differentiating hypertensive disorders of pregnancy (pregnancy induced hypertension, preeclampsia) from normal pregnancy. Methods It was a case control study. Pregnant women ?32 weeks of gestation. Study population were included 3 groups, 19 Normotensive Pregnant (NP) women as controls, 18 pregnant women with Pregnancy Induced Hypertension (PIH) and 19 with preeclampsia (PE). Serum IMA was estimated by Enzyme Linked Immune Sorbent Assay (ELISA). Results were analyzed by student ‘t’test. Critical values for serum IMA were obtained by Receiver Operation Characteristics (ROC) curves. Results Serum IMA levels were significantly elevated in PE (56.84 ± 21.57 ng/ml) when compared with PIH (36.24 ± 14.51 ng/ml) and NP (35.47 ± 11.58 ng/ml) (P value <0.001). With a cutoff of 38.33 ng/ml, sensitivity and specificity for preeclampsia was 88.9% and 73.7% respectively. Conclusions Our study demonstrated that serum IMA, an oxidative stress marker is elevated in PE & PIH. Hence serum IMA can undergo further evaluation as a marker of PE.

  12. Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension

    PubMed Central

    Nikkari, Seppo T.; Määttä, Kirsi M.; Kunnas, Tarja A.

    2015-01-01

    Abstract Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.–1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort. This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression. At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P?=?0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR?=?1.47; CI?=?1.08–2.01; P?=?0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI]?=?1.20–12.27; P?=?0.024). Those carrying variant A had also significantly higher readings of both systolic (P?=?0.047) and diastolic (P?=?0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA–GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR?=?2.01; CI?=?1.29–3.12; P?=?0.002). In conclusion, there was a significant association between iNOS genetic variant (rs2779249) and hypertension in the genetically homogenous Finnish population. Those who carried the rare A-allele of the gene had higher risk for hypertension already at the age of 35 years. PMID:26579803

  13. Drug-Induced Ocular Hypertension and Angle-Closure Glaucoma.

    PubMed

    Badhu, Badri P; Bhattarai, Balkrishna; Sangraula, Himal P

    2013-01-01

    The objective of this study was to review the available literature on the drugs causing ocular hypertension and glaucoma. Electronic literature search was carried out using the Web sites www.pubmed.gov and www.google.com published through the year 2011. The search words were "drug induced ocular hypertension" and "drug induced glaucoma" used in combination. The articles published or translated into English were studied. Quite a significant number of drugs commonly prescribed by various physicians of different specialties can induce ocular hypertension or glaucoma. A brief account of various drugs that can induce ocular hypertension has been given in this article. Those drugs are parasympatholytics; steroids; anticholinergics, adrenergics, and antidepressants; cholinomimetics; antineoplastic agents; antipsychotic and antiparkinsonism agents; H1 and H2 receptor blockers; botulinum toxin, cardiac agents, and anticoagulants; silicone oil; sulfa drugs; and anesthetic agents. Rational use of these drugs and knowledge of their potential adverse effects can help prevent the devastating complications resulting in loss of vision and compromised quality of life. PMID:26108110

  14. Regional anesthesia in patients with pregnancy induced hypertension

    PubMed Central

    Ankichetty, Saravanan P; Chin, Ki Jinn; Chan, Vincent W; Sahajanandan, Raj; Tan, Hungling; Grewal, Anju; Perlas, Anahi

    2013-01-01

    Pregnancy induced hypertension is a hypertensive disorder, which occurs in 5% to 7% of all pregnancies. These parturients present to the labour and delivery unit ranging from gestational hypertension to HELLP syndrome. It is essential to understand the various clinical conditions that may mimic preeclampsia and the urgency of cesarean delivery, which may improve perinatal outcome. The administration of general anesthesia (GA) increases morbidity and mortality in both mother and baby. The provision of regional anesthesia when possible maintains uteroplacental blood flow, avoids the complications with GA, improves maternal and neonatal outcome. The use of ultrasound may increase the success rate. This review emphasizes on the regional anesthetic considerations when such parturients present to the labor and delivery unit. PMID:24249977

  15. 76 FR 76432 - Notice of Proposed Information for Public Comment for: Capture Energy Efficiency Measures for PIH

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-07

    ...Public Comment for: Capture Energy Efficiency Measures for PIH AGENCY: Office...HUD is creating the Capture Energy Efficiency Measures for PIH (CEEMP) data...Title of Proposal: Capture Energy Efficiency Measures for PIH...

  16. Brain amines in glucocorticoid-induced hypertension in the rat.

    PubMed

    Fanelli, M; Nahmod, V E; Torres, N; Santajuliana, D; García, S I; Finkielman, S; Pirola, C J

    1992-02-01

    A two week administration of the glucocorticoid betametasone to male Wistar rats produced a mild hypertensive state. The brain of these rats showed some significant changes in amine and metabolite content with respect to normotensive controls. Epinephrine and metanephrine were increased in the rostral ventrolateral medulla and in the preoptic area. Epinephrine also increased in the septal area. Normetanephrine decreased in the rostral ventrolateral medulla. Dopamine and homovanillic acid increased in septal and preoptic areas. Dopamine alone increased in rostral ventrolateral medulla. Serotonin and 5-hydroxyindole-3-acetic acid increased in the septal area and dorsal medulla. These changes suggest significant alterations in the aminergic activity of the brain circuitry known to regulate cardiovascular functions; the changes may play a basic role in the development and maintenance of glucocorticoid-induced hypertension. PMID:1625793

  17. TIMP3 is the primary TIMP to regulate agonist-induced vascular remodelling and hypertension

    E-print Network

    MacMillan, Andrew

    3 is the primary TIMP to regulate agonist- induced vascular remodelling and hypertension Ratnadeep Hypertension is accompanied by structural remodelling of vascular extracellular matrix (ECM). Tissue inhibitor. In response to a hypertensive stimulus, the balance between MMPs and TIMPs is altered. We examined the role

  18. Soluble Epoxide Hydrolase Inhibition Protects the Kidney from Hypertension-Induced Damage

    E-print Network

    Hammock, Bruce D.

    Soluble Epoxide Hydrolase Inhibition Protects the Kidney from Hypertension-Induced Damage XUEYING hypertension in- duced renal damage. Chronic administration of the specific SEH inhibitor 1-cyclohexyl-3-dodecylurea (CDU, 3 mg/d) for 10 d lowered BP in angiotensin hypertensive rats. The contri- bution of renal

  19. Hypertension.

    PubMed

    Poulter, Neil R; Prabhakaran, Dorairaj; Caulfield, Mark

    2015-08-22

    Raised blood pressure is the biggest single contributor to the global burden of disease and to global mortality. The numbers of people affected and the prevalence of high blood pressure worldwide are expected to increase over the next decade. Preventive strategies are therefore urgently needed, especially in less developed countries, and management of hypertension must be optimised. Genetic advances in some rare causes of hypertension have been made lately, but the aggregate effect on blood pressure of all the genetic loci identified to date is small. Hence, intervention on key environmental determinants and effective implementation of trial-based therapies are needed. Three-drug combinations can control hypertension in about 90% of patients but only if resources allow identification of patients and drug delivery is affordable. Furthermore, assessment of optimal drug therapy for each ethnic group is needed. PMID:25832858

  20. Cardiovascular effects induced by linalool in normotensive and hypertensive rats.

    PubMed

    Anjos, Paulo J C; Lima, Aline O; Cunha, Patrícia S; De Sousa, Damião P; Onofre, Alexandre S C; Ribeiro, Thais P; Medeiros, Isac A; Antoniolli, Angelo R; Quintans-Júnior, Lucindo J; Santosa, Márcio R V

    2013-01-01

    Linalool is a monoterpene alcohol and constituent of several Brazilian aromatic medicinal plants, popularly used against hypertension. Cardiovascular effects induced by linalool were evaluated. In normotensive rats, (+/-)-linalool [1, 5, 10, and 20 mg/kg body weight (BW); intravenous (i.v.)]-induced hypotension was associated with tachycardia, which was attenuated by atropine (2 mg/kg BW) and N(G)-nitro-L-arginine methyl ester (20 mg/kg BW), but was not modified after indomethacin (5 mg/kg BW) administration. In hypertensive rats, linalool [200 mg/kg BW; oral (v.o.)] reduced blood pressure without changing the heart rate. In intact rings of rat mesenteric artery precontracted with 10 microM phenylephrine, linalool (from 6.4 x 10(-6) to 6.4 x 10(-3) M) induced relaxations in a concentration-dependent manner [E(max) = (115 +/- 13)%] that were not changed after atropine administration [E(max) = (105 +/- 2)%], and were not different from those obtained in endothelium-denuded rings precontracted with phenylephrine [E(max) = (108 +/- 7)%] or 80 mM KCl [E(max) = (113 +/- 7)%] or tetraethylammonium incubation [E(max) = (105 +/- 12)%]. Linalool (1.9 x 10(-3) M) antagonized the contractions induced by CaCl2 (3 x 10(-6)-10(-2) M) (maximal inhibition, 81%). Furthermore, linalool inhibited the contractions induced by 10 microM phenylephrine or 20 mM caffeine. In conclusion, these results demonstrate that linalool reduces blood pressure probably due to a direct effect on the vascular smooth muscle leading to vasodilation. PMID:23923614

  1. Pregnancy-induced hypertension in rats with early adriamycin nephropathy.

    PubMed

    Bernheim, J; Podjarny, E; Pomeranz, A; Feldman, V; Gonen, O; Rathaus, M

    1994-01-01

    In up to 60% of women with chronic renal disease an elevation of blood pressure is seen during pregnancy. The pathogenesis of this complication may be related to a diminished synthesis of vasodilatory substances by endothelial cells and to an increased sensitivity to vasopressor hormones such as angiotensin II. Previous experimental studies in rats with early chronic renal disease (adriamycin nephropathy, AN) have shown that this pregnancy-induced hypertension is associated with a lowered synthesis of glomerular PGE2. In the present study the vascular response to vasoactive substances was evaluated. In AN rats the sensitivity to an acute infusion of angiotensin II was augmented, whilst it was blunted in normal pregnant rats. Chronic treatment with the thromboxane-(Tx)-receptor antagonist, daltroban (60 mg/kg/day, p.o.) administered from mid-pregnancy induced a similar reduction in blood pressure in both AN virgin and pregnant rats. This suggests that adriamycin per se may induce vascular damage which may interfere with the normal vascular adaptation to pregnancy. Stimulation of NO synthesis with L-arginine decreased MAP values significantly in PAN rats but did not modify them during normal pregnancy. In additional experimental inhibition of the endothelial-derived relaxing factor (EDRF), nitric oxide (NO) synthesis with NAME from mid-pregnancy significantly increased SBP and MAP in normal rats. By contrast, in PAN rats chronic NAME treatment had no effect. In summary, the development of hypertension in pregnant rats with AN may be associated to endothelial cell dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8072719

  2. Regulation of Hypoxia-induced Pulmonary Hypertension by Vascular Smooth Muscle Hypoxia-Inducible Factor-1?

    PubMed Central

    Ball, Molly K.; Waypa, Gregory B.; Mungai, Paul T.; Nielsen, Jacqueline M.; Czech, Lyubov; Dudley, V. Joseph; Beussink, Lauren; Dettman, Robert W.; Berkelhamer, Sara K.; Steinhorn, Robin H.; Shah, Sanjiv J.

    2014-01-01

    Rationale: Chronic hypoxia induces pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy. At present, little is known about mechanisms driving these responses. Hypoxia-inducible factor-1? (HIF-1?) is a master regulator of transcription in hypoxic cells, up-regulating genes involved in energy metabolism, proliferation, and extracellular matrix reorganization. Systemic loss of a single HIF-1? allele has been shown to attenuate hypoxic pulmonary hypertension, but the cells contributing to this response have not been identified. Objectives: We sought to determine the contribution of HIF-1? in smooth muscle on pulmonary vascular and right heart responses to chronic hypoxia. Methods: We used mice with homozygous conditional deletion of HIF-1? combined with tamoxifen-inducible smooth muscle–specific Cre recombinase expression. Mice received either tamoxifen or vehicle followed by exposure to either normoxia or chronic hypoxia (10% O2) for 30 days before measurement of cardiopulmonary responses. Measurements and Main Results: Tamoxifen-induced smooth muscle–specific deletion of HIF-1? attenuated pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia. However, right ventricular hypertrophy was unchanged despite attenuated pulmonary pressures. Conclusions: These results indicate that HIF-1? in smooth muscle contributes to pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia. However, loss of HIF-1 function in smooth muscle does not affect hypoxic cardiac remodeling, suggesting that the cardiac hypertrophy response is not directly coupled to the increase in pulmonary artery pressure. PMID:24251580

  3. Depression in Pregnancy is Associated with Pre-existing but not Pregnancy-induced Hypertension

    PubMed Central

    Katon, Wayne J.; Russo, Joan E.; Melville, Jennifer L.; Katon, Jodie; Gavin, Amelia

    2011-01-01

    Background To examine whether depression is associated with pre-existing hypertension or pregnancy-induced hypertension in a large sample of women attending a university-based obstetrics clinic. Methods In this prospective study, participants were 2398 women receiving ongoing prenatal care at a university-based obstetrics clinic from January 2004 through January 2009. Prevalence of depression was measured using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria based on the Patient Health Questionnaire-9 as well as the self-reported use of antidepressant medication. Evidence of pre-existing hypertension, pregnancy-induced hypertension and preeclampsia/eclampsia was determined by obstetrician ICD-9 codes. Logistic regression was used to quantify the association between hypertension in pregnancy and antenatal depression. Results After adjusting for sociodemographic variables, chronic medical conditions, smoking and prior pregnancy complications, women with pre-existing hypertension had an increased risk of Any Depression (minor, major, use of antidepressants) (OR = 1.55, 95% CI 1.08, 2.23) and Major Depression and/or use of antidepressants) (OR = 1.65, 95% CI 1.10, 2.48) compared to women without hypertension. No differences were seen in risk of depression in women with pregnancy-induced hypertension or preeclampsia/eclampsia compared to those without hypertension. Conclusion Women with pre-existing hypertension, but not pregnancy induced hypertension are more likely to meet criteria for an antenatal depressive disorder and/or to be treated with antidepressants and could be targeted by obstetricians for screening for depression and enhanced treatment. PMID:22055108

  4. Effect of magnesium on vascular reactivity in NOS inhibition-induced hypertension.

    PubMed

    Basral?, Filiz; Nas?rc?lar Ülker, Seher; Koçer, Günnur; Ülker Karadamar, P?nar; Özyurt, Dilek; Cengiz, Melike; Kemal ?entürk, Ümit

    2015-06-01

    This study investigated the effect of magnesium on the vascular reactivity of conduit and resistance arteries in a nitric oxide synthase inhibition-induced hypertension model. The aorta and third-order branches of the mesenteric artery were dissected from normotensive control and hypertensive rats, and their constriction and dilation responses in physiological saline solution containing normal (1.2 mM) or high (4.8 mM) magnesium concentrations were examined. The responses of the vessels were evaluated using potassium chloride (KCl) and phenylephrine (Phe), acetylcholine (ACh) and sodium nitroprusside. The Phe-induced constriction response of the aortic rings increased, whereas the ACh-induced dilation response decreased, in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium did not alter these responses in either group. Both the KCl- and Phe-induced constriction responses of the mesenteric arteries increased, and the ACh-induced dilation response decreased in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium significantly decreased the KCl and Phe-induced constriction and increased the ACh-induced dilation response of the mesenteric arteries in the hypertensive group, while it did not alter these responses in controls. This study suggests that high magnesium improves vascular reactivity of resistance-, but not conduit-type arteries in the nitric oxide synthase inhibition-induced hypertension model. PMID:26395418

  5. Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations.

    PubMed

    Blázquez-Medela, Ana M; García-Sánchez, Omar; Quirós, Yaremi; Blanco-Gozalo, Victor; Prieto-García, Laura; Sancho-Martínez, Sandra M; Romero, Miguel; Duarte, Juan M; López-Hernández, Francisco J; López-Novoa, José M; Martínez-Salgado, Carlos

    2015-10-01

    Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys.We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage.Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments.The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening.KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage. PMID:26469898

  6. Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations

    PubMed Central

    Blázquez-Medela, Ana M.; García-Sánchez, Omar; Quirós, Yaremi; Blanco-Gozalo, Victor; Prieto-García, Laura; Sancho-Martínez, Sandra M.; Romero, Miguel; Duarte, Juan M.; López-Hernández, Francisco J.; López-Novoa, José M.; Martínez-Salgado, Carlos

    2015-01-01

    Abstract Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys. We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage. Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments. The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening. KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage. PMID:26469898

  7. Aging exacerbates hypertension-induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection

    PubMed Central

    Toth, Peter; Tarantini, Stefano; Springo, Zsolt; Tucsek, Zsuzsanna; Gautam, Tripti; Giles, Cory B; Wren, Jonathan D; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-01-01

    Recent studies demonstrate that aging exacerbates hypertension-induced cognitive decline, but the specific age-related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension-induced CMHs young (3 months) and aged (24 months) mice were treated with angiotensin II plus L-NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension-induced cerebrovascular oxidative stress and redox-sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension-induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension-induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high-risk elderly patients. PMID:25677910

  8. Neutralization by insulin of the hypertensive effect of dermcidin isoform 2: an environmentally induced diabetogenic and hypertensive protein.

    PubMed

    Ghosh, Rajeshwary; Bank, Sarbashri; Bhattacharya, Rabindra; Khan, Nighat N; Sinha, A Kumar

    2014-01-01

    The effect of dermcidin isoform 2 (dermcidin), an environmentally induced stress protein, was investigated on the genesis of diabetes mellitus and hypertension, the two major atherosclerotic risk factors. The role of dermcidin as an atherosclerotic risk factor related to the impaired systemic insulin level was investigated. Dermcidin was prepared by electrophoresis using plasma from the subjects with acute ischemic heart disease. Injection of 0.2??M dermcidin in mice increased the blood glucose level from 98 ± 2.45?mg/dL to 350? ± 10.2?mg/dL which was normalized by the oral administration of acetyl salicylic acid (aspirin) after 24?h. Hypertensive subjects with systolic and diastolic blood pressure of 165?mm and 95?mm of Hg, respectively, had plasma dermcidin level of 95?nM. Ingestion of acetyl salicylic acid (aspirin) (150?mg/70?kg body weight) decreased the systolic and diastolic pressures to 125?mm and 80?mm of Hg, respectively, with decrease of dermcidin level to 15?nM. Incubation of kidney cortex cells with 0.2??M dermcidin-inhibited synthesis of (r)-cortexin, an antihypertensive protein, and the basal (r)-cortexin level was reduced from 33?nM to 15?nM. Addition of 25??units of insulin/mL was found to reverse the inhibition of cortexin synthesis. The effect of dermcidin as a diabetogenic and a hypertensive agent could be controlled either by aspirin or by insulin. PMID:24649391

  9. Hypertension-induced cerebellar encephalopathy and hydrocephalus in a male.

    PubMed

    Lin, Kuang-Lin; Hsu, Wen-Chin; Wang, Huei-Shyong; Lui, Tai-Ngar

    2006-01-01

    Hypertensive encephalopathy is believed to be caused by an abrupt elevation in systemic blood pressure. It rarely occurs in children and can be neurologically devastating if it is not recognized and treated immediately. This report describes an 11-year-old male who presented with edema and a cerebellar lesion, with acute obstructive hydrocephalus resulting from hypertensive encephalopathy. A shunt was inserted to relieve pressure in the acute stage. The patient's hydrocephalus and cerebellar swelling subsided when his blood pressure was controlled. The cerebellar lesion had been initially diagnosed as a glioma. In children, a cerebellar lesion occurring with acute obstructive hydrocephalus and hypertensive encephalopathy is rare but reversible. Clinicians should be aware of this condition because it might be misdiagnosed as a tumor of the posterior fossa. PMID:16376285

  10. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    PubMed Central

    Cristóbal-García, Magdalena; García-Arroyo, Fernando E.; Arellano-Buendía, Abraham S.; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Zazueta, Cecilia; Johnson, Richard J.; Sánchez Lozada, Laura-Gabriela

    2015-01-01

    We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750?mg/kg BW), OA+Allopurinol (AP, 150?mg/L drinking water), OA+Tempol (T, 15?mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-?-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. PMID:25918583

  11. NLRP3 Deficiency Improves Angiotensin II-Induced Hypertension But Not Fetal Growth Restriction During Pregnancy.

    PubMed

    Shirasuna, Koumei; Karasawa, Tadayoshi; Usui, Fumitake; Kobayashi, Motoi; Komada, Tadanori; Kimura, Hiroaki; Kawashima, Akira; Ohkuchi, Akihide; Taniguchi, Shun'ichiro; Takahashi, Masafumi

    2015-11-01

    Preeclampsia is a pregnancy-specific syndrome characterized by elevated blood pressure, proteinuria, and intrauterine growth restriction (IUGR). Although sterile inflammation appears to be involved, its pathogenesis remains unclear. Recent evidence indicates that sterile inflammation is mediated through the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes, composed of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1. Here we investigated the role of the NLRP3 inflammasomes in the pathogenesis of preeclampsia using Nlrp3(-/-) and Asc(-/-) (Nlrp3 and Asc deficient) pregnant mice. During pregnancy in mice, continuous infusion of high-dose angiotensin II (AngII) induced hypertension, proteinuria, and IUGR, whereas infusion of low-dose AngII caused hypertension alone. AngII-induced hypertension was prevented in Nlrp3(-/-) mice but not in Asc(-/-), indicating that NLRP3 contributes to gestational hypertension independently of ASC-mediated inflammasomes. Although NLRP3 deficiency had no effect on IUGR, it restored the IL-6 up-regulation in the placenta and kidney of AngII-infused mice. Furthermore, treatment with hydralazine prevented the development of gestational hypertension but not IUGR or IL-6 expression in the placenta and kidney. These findings demonstrate that NLRP3 contributes to the development of gestational hypertension independently of the inflammasomes and that IUGR and kidney injury can occur independent of blood pressure elevation during pregnancy. PMID:26360504

  12. Pregnancy-induced hypertension: development of a model in the pregnant sheep.

    PubMed

    Thatcher, C D; Keith, J C

    1986-07-01

    Selected hemodynamic, renal, and biochemical parameters were assessed in chronically instrumented third-trimester pregnant ewes and in the same ewes after induction of pregnancy toxemia. Ewes with induced pregnancy toxemia developed hypertension, proteinuria, ketonuria, decreased glomerular filtration rate, decreased cardiac output, and decreased left uterine artery blood flow. Histological and transmission electron microscopy revealed the development of renal morphologic changes consistent with those observed in human pregnancy-induced hypertension. These studies have elucidated that pregnancy-induced hypertension can be produced experimentally in the pregnant ewe. Furthermore, the pathophysiologic features of ovine pregnancy toxemia are similar to those of human preeclampsia, and therefore the sheep provides a suitable animal model to study the human condition, which still remains a major complication of pregnancy, jeopardizing both mother and fetus. PMID:3728588

  13. Asiatic acid alleviates cardiovascular remodelling in rats with L-NAME-induced hypertension.

    PubMed

    Bunbupha, Sarawoot; Prachaney, Parichat; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Welbat, Jariya Umka; Pakdeechote, Poungrat

    2015-11-01

    A previous study demonstrated the antihypertensive effect of asiatic acid. The current study investigates the effect of asiatic acid on cardiovascular remodelling and possible mechanisms involved in N? -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg per day) for 3 weeks in order to induce hypertension. Hypertensive rats were administered asiatic acid (20 mg/kg per day) or vehicle for a further 2 weeks. It was found that hypertensive rats showed high systolic blood pressure, left ventricular (LV) hypertrophy, increases in LV fibrosis, aortic wall thickness and aortic collagen deposition (P < 0.05). Moreover, decreased plasma nitrate and nitrite (NOx) and increased plasma tumor necrosis factor alpha (TNF-?) were observed in hypertensive rats (P < 0.05). This was consistent with downregulation of endothelial nitric oxide synthase (eNOS) expression and upregulation of inducible nitric oxide synthase (iNOS) expression in heart and aortic tissues (P < 0.05). Levels of malondialdehyde (MDA) in plasma, aortic and heart tissues were significantly increased in hypertensive rats (P < 0.05). Asiatic acid markedly reduced blood pressure, alleviated cardiovascular remodelling, and restored plasma NOx and TNF-? as well as eNOS/iNOS expression in heart and aortic tissues (P < 0.05). Additionally, there was a significant reduction of MDA levels in the tissues of treated hypertensive rats. In conclusion, this study demonstrates the therapeutic effects of asiatic acid on blood pressure and cardiovascular remodelling, which is possibly related to the restoration of eNOS/iNOS expression, and the resulting anti-inflammatory and antioxidant activities. PMID:26234646

  14. Supplemental calcium and risk reduction of hypertension, pregnancy-induced hypertension, and preeclampsia: an evidence-based review by the US Food and Drug Administration.

    PubMed

    Trumbo, Paula R; Ellwood, Kathleen C

    2007-02-01

    The labeling of health claims that meet the significant scientific agreement (SSA) standard (authorized health claims) and qualified health claims on conventional foods and dietary supplements requires premarket approval by the US Food and Drug Administration (FDA). FDA conducts an evidence-based review to determine whether there is sufficient evidence to support an authorized or qualified health claim. An evidence-based review was conducted on the human intervention and observational studies evaluating the role of supplemental calcium in reducing the risk of hypertension, pregnancy-induced hypertension, and preeclampsia. This review provides FDA's evaluation of the current scientific evidence on the role of supplemental calcium in reducing the risk of these three end points. Based on this evidence-based review, the agency concluded that the relationship between calcium and risk of hypertension is inconsistent and inconclusive, and the relationship between calcium and risk of pregnancy-induced hypertension and preeclampsia is highly unlikely. PMID:17345960

  15. Resolution of pulmonary hypertension complication during venovenous perfusion-induced systemic hyperthermia application.

    PubMed

    Ballard-Croft, Cherry; Wang, Dongfang; Jones, Cameron; Wang, Jingkun; Pollock, Robert; Jubak, Bob; Topaz, Stephen; Zwischenberger, Joseph B

    2013-01-01

    We are developing a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced cancer treatment. The vv-PISH system consistently delivered hyperthermia to adult healthy swine, but significant pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent pulmonary hypertension. We hypothesized that pulmonary hypertension results from decreased priming solution air solubility, which causes pulmonary gas embolism. Healthy adult sheep (n = 3) were used to establish a standard vv-PISH sheep model without priming solution preheating. In subsequent sheep (n = 7), the priming solution was preheated (42-46°C) and the hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hours of 42°C hyperthermia. In the group lacking priming solution preheating, significant pulmonary hypertension (35-44 mm?Hg) developed. In the sheep with priming solution preheating, pulmonary artery pressure was very stable without pulmonary hypertension. Blood electrolytes were in physiologic range, and complete blood counts were unaffected by hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming solution preheating completely resolved the problem of pulmonary hypertension as a milestone toward developing a safe and easy-to-use vv-PISH system for cancer treatment. PMID:23820278

  16. The effect of ozone on blood pressure in DOCA-salt-induced hypertensive rats

    PubMed Central

    Akc?lar, Raziye; Akçer, Sezer; ?im?ek, Hasan; Akc?lar, Ayd?n; Bayat, Zeynep; Genç, Osman

    2015-01-01

    Background: Hypertension is a risk factor for the cardiovascular diseases. Ozone as a therapeutic agent for the treatment of several disorders. We aimed to observe the effects of ozone on the blood pressure in DOCA-salt hypertensive rats. Methods: Twenty three young Sprague Dawley male rats were divided into three groups; Control (C), Hypertension (H) and Hypertension + Ozone (HO). Hypertension was induced by injection of DOCA-salt (25 mg/kg, s.c.) twice weekly, 4 weeks, whereas intraperitoneal ozone was administered (1.1 mg/kg) for 10 days. Serum endothelin-1, nitric oxide and renin levels were measured with ELISA. Blood pressures were monitored using a tail cuff system. Endothelin-1, ET receptor A and ET receptor B mRNA expression in heart and vascular tissue were assessed by quantitative reverse transcription polymerase chain reaction. Results: Blood pressure, serum endothelin-1 and ET receptor A mRNA expression levels were increased in H group, whereas serum renin, nitric oxide and ET receptor B mRNA expression levels in the heart and vascular tissue decreased compared with C and HO groups, which were counteracted by ozone treatment. Conclusion: Ozone treatment decreases blood pressure and is effective in preventing the progression of hypertensive disease, the mechanisms of which are associated with anti-vasoconstrictor effects through reducing the levels of serum endothelin-1 and ET receptor A mRNA expression in the heart and vascular tissue. PMID:26550192

  17. Blockade of Salusin-? in Hypothalamic Paraventricular Nucleus Attenuates Hypertension and Cardiac Hypertrophy in Salt-induced Hypertensive Rats.

    PubMed

    Li, Hong-Bao; Qin, Da-Nian; Suo, Yu-Ping; Guo, Jing; Su, Qing; Miao, Yu-Wang; Sun, Wen-Yan; Yi, Qiu-Yue; Cui, Wei; Cheng, Kang; Zhu, Guo-Qing; Kang, Yu-Ming

    2015-10-01

    Salusin-?, a multifunctional bioactive peptide, is considered as a promising candidate biomarker for predicting cardiovascular diseases. This study was designed to determine whether inhibition of salusin-? in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by restoring neurotransmitters and cytokines. Male Sprague Dawley rats were fed with a normal salt diet (NS, 0.3%) or a high salt diet (HS, 8%) for 8 weeks to induce hypertension. Then, these rats received bilateral PVN infusion of a specific salusin-? blocker, antisalusin-? IgG (SIgG), or control IgG (CIgG) for 2 weeks. HS rats exhibited higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/bodyweight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and messenger RNA levels of cardiac atrial natriuretic peptide (ANP), and ?-myosin heavy chain. Compared with NS rats, HS rats had higher levels of glutamate, norepinephrine, tyrosine hydroxylase, proinflammatory cytokines, and lower levels of gamma-aminobutyric acid, interleukin 10, and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN, and higher plasma levels of proinflammatory cytokines. Chronic PVN infusion of SIgG attenuated all these changes in HS rats. Our findings suggest that HS rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between proinflammatory and anti-inflammatory cytokines in the PVN; and chronic inhibition of salusin-? in the PVN restores neurotransmitters and cytokines in the PVN, thereby attenuating hypertensive responses and cardiac hypertrophy. PMID:26038832

  18. Antihypertensive Effect of Radix Paeoniae Alba in Spontaneously Hypertensive Rats and Excessive Alcohol Intake and High Fat Diet Induced Hypertensive Rats

    PubMed Central

    Su-Hong, Chen; Qi, Chen; Bo, Li; Jian-Li, Gao; Jie, Su; Gui-Yuan, Lv

    2015-01-01

    Radix Paeoniae Alba (Baishao, RPA) has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD-) induced hypertensive rats and spontaneously hypertensive rats (SHR) was constantly received either RPA extract (25 or 75?mg/kg) or captopril (15?mg/kg) all along the experiments. As a result, RPA extract (75?mg/kg) could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO) and endothelin (ET) levels. PMID:25784949

  19. Dimethylarginine dimethylaminohydrolase-1 mediates inhibitory effect of interleukin-10 on angiotensin II-induced hypertensive effects in vascular smooth muscle cells of spontaneously hypertensive rats.

    PubMed

    Kim, Hye Young; Kim, Hee Sun

    2016-01-01

    In hypertension studies, anti-inflammatory cytokine interleukin-10 (IL-10) has been shown to prevent angiotensin II (Ang II)-induced vasoconstriction and regulate vascular function by down-regulating pro-inflammatory cytokine and superoxide production in vascular cells. However, little is known about the mechanism behind the down-regulatory effect of IL-10 on Ang II-induced hypertensive mediators. In this study, we demonstrated the effects of IL-10 on expression of dimethylarginine dimethylaminohydrolase (DDAH)-1, a regulator of NO bioavailability, as well as the down-regulatory mechanism of action of IL-10 in relation to Ang II-induced hypertensive mediator expression and cell proliferation in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). IL-10 increased DDAH-1 but not DDAH-2 expression and increased DDAH activity. Additionally, IL-10 attenuated Ang II-induced DDAH-1 inhibition in SHR VSMCs. Increased DDAH activity due to IL-10 was mediated mainly through Ang II subtype II receptor (AT2 R) and AMP-activated protein kinase (AMPK) activation. DDAH-1 induced by IL-10 partially mediated the inhibitory action of IL-10 on Ang II-induced 12-lipoxygenase (LO) and endothelin (ET)-1 expression in SHR VSMCs. In addition, the inhibitory effect of IL-10 on proliferation of Ang II-induced VSMCs was mediated partially via DDAH-1 activity. These results suggest that DDAH-1 plays a potentially important role in the anti-hypertensive activity of IL-10 during Ang II-induced hypertension. PMID:26375520

  20. Hepatoprotective Effect of Silymarin (Silybum marianum) on Hepatotoxicity Induced by Acetaminophen in Spontaneously Hypertensive Rats

    PubMed Central

    Cardia, Gabriel Fernando Esteves; da Rocha, Bruno Ambrósio; Aguiar, Rafael Pazzinatto; Spironello, Ricardo Alexandre; Caparroz-Assef, Silvana Martins; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2015-01-01

    This study was aimed to investigate the effect of Silymarin (SLM) on the hypertension state and the liver function changes induced by acetaminophen (APAP) in spontaneously hypertensive rat (SHR). Animals normotensive (N) or hypertensive (SHR) were treated or not with APAP (3?g/kg, oral) or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), gamma glutamyl transferase (?-GT), and alkaline phosphatase (ALP) of all groups, were determined. Liver injury was assessed using histological studies. Samples of their livers were then used to determine the myeloperoxidase (MPO) activity and nitric oxide (NO) production and were also sectioned for histological analysis. No differences were observed for ALT, ?-GT, and GLU levels between SHR and normotensive rats groups. However, AST and ALP levels were increased in hypertensive animals. APAP treatment promoted an increase in ALT and AST in both SHR and N. However, only for SHR, ?-GT levels were increased. The inflammatory response evaluated by MPO activity and NO production showed that SHR was more susceptible to APAP effect, by increasing leucocyte infiltration. Silymarin treatment (Legalon) restored the hepatocyte functional and histopathological alterations induced by APAP in normotensive and hypertensive animals. PMID:25821491

  1. Response of the adrenergic system in the cadmium-induced hypertensive rat

    SciTech Connect

    Revis, N.W.; Major, T.C.; Horton, C.Y.

    1983-01-01

    Previous investigators, using an in vitro system, have shown that cadmium inhibits neuronal uptake of norepinephrine (NE). The current studies were performed to determine if the adrenergic system is altered in the cadmium-induced hypertensive rat. The results show that the Fischer and Sprague-Dawley rats develop hypertension, whereas the Wistar normotensive and Wistar hypertensive rats develop hypotension when exposed to 5 ppm of cadmium via drinking water. Results from these studies also show that in the cadmium-induced hypertensive rat, plasma NE is significantly elevated and that plasma clearance of (/sup 3/H)NE is significantly reduced. However, the changes in NE metabolism observed in the hypertensive rats were also observed in hypotensive rats. Furthermore in the Wistar strain, renal artery cadmium levels were significantly higher than observed in the other two strains. The authors suggest that the direction of change in blood following cadmium treatment is associated with both the plasma level of norepinephrine and the arterial level of cadmium.

  2. Renal Transcriptome Analysis of Programmed Hypertension Induced by Maternal Nutritional Insults.

    PubMed

    Tain, You-Lin; Hsu, Chien-Ning; Chan, Julie Y H; Huang, Li-Tung

    2015-01-01

    Maternal nutrition can affect development, leading to long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether alterations in renal transcriptome are responsible for generating programmed hypertension among four different models using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received 50% caloric restriction (CR), intraperitoneal injection of 45 mg/kg streptozotocin, 60% high-fructose (HF) diet, or 1% NaCl in drinking water to conduct CR, diabetes, HF, or high-salt models, respectively. All four models induced programmed hypertension in adult male offspring. We observed 16 shared genes in a two-week-old kidney among four different models. The identified differential expressed genes (DEGs) that are related to the regulation of blood pressure included Adrb3, Alb, Apoe, Calca, Kng1, Adm2, Guca2b, Hba2, Hba-a2, and Ppara. The peroxisome proliferator-activated receptor (PPAR) signaling pathway and glutathione metabolism pathway were shared by the CR, diabetes, and HF models. Conclusively, a variety of maternal nutritional insults induced the same phenotype-programmed hypertension with differential alterations of renal transcriptome in adult male offspring. The roles of DEGs identified by the NGS in this study deserve further clarification to develop ideal maternal dietary interventions and thus spare the next generations from the burden of hypertension. PMID:26247937

  3. Hypertension-induced reversible posterior leukoencephalopathy syndrome causing obstructive hydrocephalus.

    PubMed

    Lee, S Y; Dinesh, S K; Thomas, J

    2008-04-01

    Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized clinically by headache, altered mental status, abnormal visual perception and seizures. It is associated with neuroradiological findings characterized by reversible white matter abnormalities, predominantly in the parietal-occipital areas. Since the first description in 1996, it has been recognized in an increasing number of medical conditions, including hypertensive encephalopathy, eclampsia, and immunosuppressive treatment. The rapid resolution of clinical and neuroradiologic abnormalities suggests cerebral oedema, which is thought to result from impaired cerebrovascular autoregulation and endothelial injury. We report a patient presenting with acute onset progressively worsening headache and confusion associated with uncontrolled hypertension. CT and MRI revealed acute non-communicating hydrocephalus secondary to cerebellar and pontine oedema. The patient became drowsy, so an external ventricular drain was inserted for decompression of the acute hydrocephalus, and his blood pressure was aggressively managed. The patient recovered well with complete clinical and radiological resolution. This case illustrates the reversibility of RPLS if it is diagnosed early and appropriate treatment is instituted. PMID:18249121

  4. Total exchangeable sodium in rats with mestranol-induced hypertension

    SciTech Connect

    Abas, N. ); Johnson, J.A. )

    1989-05-01

    Rats were fed a diet containing mestranol, an orally active estrogen, while control rats were fed the same diet without mestranol. After 6 months of these diets, the rats were weighed, blood pressures were measured, and total exchangeable sodium was determined by injecting {sup 24}Na and determining the amount of {sup 24}Na in the plasma, the plasma Na concentration, and the residual {sup 24}Na in each rat. The 16 mestranol-treated rats were hypertensive (mean arterial pressure 135 {plus minus} 3 mm Hg) when compared with the 17 controls (116 {plus minus} 3 mm Hg). Total exchangeable sodium in the mestranol-treated rats averaged 39.94 {plus minus} 0.49 (SEM) mEq/kg body wt, which was very similar to the value of 39.87 {plus minus} 0.63 mEq/kg found in the control rats. Thus, no changes in total exchangeable sodium in mestranol-hypertensive rats were found in these studies.

  5. Pharmacological treatment of antipsychotic-induced dyslipidemia and hypertension.

    PubMed

    Tse, Lurdes; Procyshyn, Ric M; Fredrikson, Diane H; Boyda, Heidi N; Honer, William G; Barr, Alasdair M

    2014-05-01

    Second-generation antipsychotics (SGAs) are associated with significant comorbid metabolic abnormalities. Adjunct medications may be prescribed to treat these metabolic side effects, but the evidence supporting this practice (especially for the management of antipsychotic-associated dyslipidemia and hypertension) is limited. The purpose of this review was to evaluate the effects of adjunct medications on triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein, and blood pressure levels in participants taking SGAs for psychosis. Studies were systematically searched and evaluated. Studies were included for review if participants were taking SGAs and if lipid and/or blood pressure levels were included as outcome measures. Statins, conventional lipid-lowering agents, fluvoxamine, ramelteon, topiramate, valsartan, telmisartan, omega-3 fatty acids, metformin (including both immediate-release and extended-release formulations), and a combination of metformin-sibutramine seemed to have beneficial effects on lipid levels. Valsartan, telmisartan, and topiramate appeared to be effective for controlling increases in blood pressure. The literature on adjunct medications for the treatment of antipsychotic-associated dyslipidemia and hypertension is not exhaustive, and long-term randomized-controlled trials would offer valuable results. PMID:24169026

  6. [Modern methods of early screening for preeclampsia and pregnancy-induced hypertension--a review].

    PubMed

    Poprawski, Grzegorz; Wender-Ozegowska, Ewa; Zawiejska, Agnieszka; Brazert, Jacek

    2012-09-01

    Preeclampsia remains to be a serious perinatal complication and early screening for this disease to identify the high risk population before the first symptoms develop constitutes a considerable clinical challenge. Modern methods of screening for preeclampsia and pregnancy-induced hypertension include patients history biochemical serum markers and foetal DNA and RNA in maternal serum. They aid the process of developing an optimal protocol to initiate treatment in early pregnancy and to reduce the rate of complications. Our review presents an overview of the novel methods and techniques used for early screening for preeclampsia and pregnancy-induced hypertension. Most of the research focuses on 11-13 weeks of gestation due to the fact that the first prenatal examination is performed at that time. The most important information seems to be: weight, mass, mean blood pressure, history of pregnancy-induced hypertension or preeclampsia at previous pregnancies as well as the ethnic origin. During an ultrasound scan, pulsatility index of the uterine arteries is measured. Blood samples are obtained during the last part of the examination. At the moment only a few markers seem to be strong predictors of hypertensive disorders during pregnancy: pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Also, fetal DNA and RNA in maternal plasma are helpful in the prediction of preeclampsia as they are markers of the trophoblast apoptosis. Researchers aim at identifying the population at high risk of pregnancy-induced hypertension and preeclampsia in order to offer appropriate antenatal care to these women. At the moment many drugs and diet supplements are investigated to reduce the prevalence of hypertensive disorders in pregnancy. These medications are usually administrated in early gestation (up to 16 week of gestation) before the first clinical symptoms present. Low doses of aspirin were found to decrease the risk of preeclampsia in high-risk groups. Moreover, according to some recent research, also essential omega-3 fatty acids reduce the incidence of preeclampsia. None of the other investigated diet supplements or antioxidants were proven to successfully reduce incidents of hypertensive disorders. So far, there is available evidence on the lack of any effect for vitamines C, D or E. Further studies are necessary to define clinical useful markers of gestational hypertension. PMID:23342898

  7. Dasatinib-induced pulmonary hypertension in acute lymphoblastic leukemia: case report.

    PubMed

    Taçoy, Gülten; Çengel, Atiye; Özkurt, Zübeyde Nur; Türko?lu, Sedat

    2015-01-01

    Pulmonary hypertension (PHT) is a pathological condition determined as an increase in mean pulmonary arterial pressure ?25 mmHg. Pulmonary arterial hypertension (PAH) is precapillary PHT and a life-threatening disease group which consists of different etiologies with the same pathological and clinical findings, and which is characterized by elevated pulmonary vascular resistance. Dasatinib is a dual Src/Abl kinase inhibitor associated with higher affinity for BCR/ABL kinase than imatinib, and is used in the treatment of chronic myelocytic leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). We describe a case with ALL, in whom dasatinib treatment induced PAH, and who recovered with bosentan treatment. PMID:25655855

  8. Primary hypertension-induced cerebellar encephalopathy causing obstructive hydrocephalus. Case report.

    PubMed

    Verrees, Meg; Fernandes Filho, Jose Americo; Suarez, Jose I; Ratcheson, Robert A

    2003-06-01

    Hypertension-induced encephalopathy is a recognized pathological process commonly focused in the parietal and occipital lobes of the cerebral hemispheres. The parenchyma of the posterior fossa is infrequently involved. The authors report on two cases of isolated edema of the cerebellar hemispheres, which occurred in the setting of hypertensive crisis and led to complete obstruction of or significant impingement on the fourth ventricle and potentially lethal hydrocephalus. To the best of the authors' knowledge, these are the first reported cases of hypertensive encephalopathy centered in the posterior fossa. Two patients presented with profound decreases in neurological status subsequent to development of malignant hypertension. Imaging studies revealed diffusely edematous cerebellar hemispheres with effacement of the fourth ventricle, causing dilation of the lateral and third ventricles. Following emergency placement of external ventricular drains, control of systemic blood pressure was accomplished, and neurological functioning returned to baseline. Although neurological deterioration resolved swiftly following placement of ventricular catheters and administration of diuretic agents, systemic blood pressure did not fluctuate with the release of cerebrospinal fluid and resolution of increased intracranial pressure. Decrease in systemic blood pressure lagged well behind improvement in neurological status; the patients remained morbidly hypertensive until systemic blood pressure was controlled with multiple parenteral medications. The authors hypothesize that the development of hypertension beyond the limits of cerebral autoregulation led to breakdown of the blood-brain barrier in the cerebellum and development of posterior fossa edema secondary to the focal transudation of protein and fluid. Correction of the elevated blood pressure led to amelioration of cerebellar edema. In the appropriate clinical setting, hypertension as the inciting cause of cerebellar encephalopathy should be considered. PMID:12816279

  9. Oxidant and enzymatic antioxidant status (gene expression and activity) in the brain of chickens with cold-induced pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Hassanpour, Hossein; Khalaji-Pirbalouty, Valiallah; Nasiri, Leila; Mohebbi, Abdonnaser; Bahadoran, Shahab

    2015-11-01

    To evaluate oxidant and antioxidant status of the brain (hindbrain, midbrain, and forebrain) in chickens with cold-induced pulmonary hypertension, the measurements of lipid peroxidation, protein oxidation, antioxidant capacity, enzymatic activity, and gene expression (for catalase, glutathione peroxidase, and superoxide dismutases) were done. There were high lipid peroxidation/protein oxidation and low antioxidant capacity in the hindbrain of cold-induced pulmonary hypertensive chickens compared to control ( P < 0.05). In the hypertensive chickens, superoxide dismutase activity was decreased (forebrain, midbrain, and hindbrain), while catalase activity was increased (forebrain and midbrain) ( P < 0.05). Glutathione peroxidase activity did not change. Relative gene expression of catalase and superoxide dismutases (1 and 2) was downregulated, while glutathione peroxidase was upregulated in the brain of the cold-induced pulmonary hypertensive chickens. Probably, these situations in the oxidant and antioxidant status of the brain especially hindbrain may change its function at cardiovascular center and sympathetic nervous system to exacerbate pulmonary hypertension.

  10. Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat

    PubMed Central

    Regal, Jean F.; Lillegard, Kathryn E.; Bauer, Ashley J.; Elmquist, Barbara J.; Loeks-Johnson, Alex C.; Gilbert, Jeffrey S.

    2015-01-01

    Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise. Using the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia-induced hypertension in the rat, we determined the effect of neutrophil depletion on blood pressure and fetal resorptions. Neutrophils were depleted with repeated injections of polyclonal rabbit anti-rat polymorphonuclear leukocyte (PMN) antibody (antiPMN). Rats received either antiPMN or normal rabbit serum (Control) on 13.5, 15.5, 17.5, and 18.5 days post conception (dpc). On 14.5 dpc, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP). On 18.5 dpc, carotid arterial catheters were placed and mean arterial pressure (MAP) was measured on 19.5 dpc. Neutrophil-depleted rats had reduced circulating neutrophils from 14.5 to 19.5 dpc compared to Control, as well as decreased neutrophils in lung and placenta on 19.5 dpc. MAP increased in RUPP Control vs Sham Control rats, and neutrophil depletion attenuated this increase in MAP in RUPP rats without any effect on Sham rats. The RUPP-induced increase in fetal resorptions and complement activation product C3a were not affected by neutrophil depletion. Thus, these data are the first to indicate that neutrophils play an important role in RUPP hypertension and that cells of the innate immune system may significantly contribute to pregnancy-induced hypertension. PMID:26135305

  11. Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat.

    PubMed

    Regal, Jean F; Lillegard, Kathryn E; Bauer, Ashley J; Elmquist, Barbara J; Loeks-Johnson, Alex C; Gilbert, Jeffrey S

    2015-01-01

    Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise. Using the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia-induced hypertension in the rat, we determined the effect of neutrophil depletion on blood pressure and fetal resorptions. Neutrophils were depleted with repeated injections of polyclonal rabbit anti-rat polymorphonuclear leukocyte (PMN) antibody (antiPMN). Rats received either antiPMN or normal rabbit serum (Control) on 13.5, 15.5, 17.5, and 18.5 days post conception (dpc). On 14.5 dpc, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP). On 18.5 dpc, carotid arterial catheters were placed and mean arterial pressure (MAP) was measured on 19.5 dpc. Neutrophil-depleted rats had reduced circulating neutrophils from 14.5 to 19.5 dpc compared to Control, as well as decreased neutrophils in lung and placenta on 19.5 dpc. MAP increased in RUPP Control vs Sham Control rats, and neutrophil depletion attenuated this increase in MAP in RUPP rats without any effect on Sham rats. The RUPP-induced increase in fetal resorptions and complement activation product C3a were not affected by neutrophil depletion. Thus, these data are the first to indicate that neutrophils play an important role in RUPP hypertension and that cells of the innate immune system may significantly contribute to pregnancy-induced hypertension. PMID:26135305

  12. Baroreflex deficit blunts exercise training-induced cardiovascular and autonomic adaptations in hypertensive rats.

    PubMed

    Moraes-Silva, I C; De La Fuente, R N; Mostarda, C; Rosa, K; Flues, K; Damaceno-Rodrigues, N R; Caldini, E G; De Angelis, K; Krieger, E M; Irigoyen, M C

    2010-03-01

    1. Baroreceptors regulate moment-to-moment blood pressure (BP) variations, but their long-term effect on the cardiovascular system remains unclear. Baroreceptor deficit accompanying hypertension contributes to increased BP variability (BPV) and sympathetic activity, whereas exercise training has been associated with an improvement in these baroreflex-mediated changes. The aim of the present study was to evaluate the autonomic, haemodynamic and cardiac morphofunctional effects of long-term sinoaortic baroreceptor denervation (SAD) in trained and sedentary spontaneously hypertensive rats (SHR). 2. Rats were subjected to SAD or sham surgery and were then further divided into sedentary and trained groups. Exercise training was performed on a treadmill (five times per week, 50-70% maximal running speed). All groups were studied after 10 weeks. 3. Sinoaortic baroreceptor denervation in SHR had no effect on basal heart rate (HR) or BP, but did augment BPV, impairing the cardiac function associated with increased cardiac hypertrophy and collagen deposition. Exercise training reduced BP and HR, re-established baroreflex sensitivity and improved both HR variability and BPV. However, SAD in trained SHR blunted all these improvements. Moreover, the systolic and diastolic hypertensive dysfunction, reduced left ventricular chamber diameter and increased cardiac collagen deposition seen in SHR were improved after the training protocol. These benefits were attenuated in trained SAD SHR. 4. In conclusion, the present study has demonstrated that the arterial baroreflex mediates cardiac disturbances associated with hypertension and is crucial for the beneficial cardiovascular morphofunctional and autonomic adaptations induced by chronic exercise in hypertension. PMID:19930428

  13. Effects of Atorvastatin on the Hypertension-Induced Oxidative Stress in the Rat Brain

    PubMed Central

    Mohammadi, Mohammad Taghi; Amini, Reza; Jahanbakhsh, Zahra; Shekarforoush, Shahnaz

    2013-01-01

    Background: It is well known that the development of brain oxidative stress is one of the most serious complications of arterial hypertension that evokes brain tissue damage. The aim of this study was to examine the effects of atorvastatin treatment (20 mg/kg/day), as an antioxidant, to prevent the brain tissue oxidative stress in the hypertensive (HTN) rats. Methods: Experiments were performed in four groups of rats (n = 5 each group): sham, sham-treated, HTN and HTN treated. Rats were made HTN by aortic constriction above the renal arteries. After 30 days, rats were slaughtered under deep anesthesia to remove brain hemispheres. After tissue homogenization, enzyme activities of superoxide dismutase (SOD) and catalase (CAT), as well as glutathione (GSH) content and malondialdehyde (MDA) level were determined by biochemical methods. Results: In HTN rats, arterial blood pressure was increased about 40% and brain enzyme activities of SOD and CAT were significantly decreased compared with sham group. Induction of hypertension significantly decreased GSH content and increased MDA level of brain tissue. Treatment with atorvastatin enhanced the activity of SOD and prevented from GSH decrement during hypertension. Conclusion: Based on the findings of this study, treatment with atorvastatin might have saved the brain tissue of HTN rats from hypertension-induced oxidative stress. PMID:23748894

  14. Complement activation is critical for placental ischemia-induced hypertension in the rat.

    PubMed

    Lillegard, Kathryn E; Johnson, Alex C; Lojovich, Sarah J; Bauer, Ashley J; Marsh, Henry C; Gilbert, Jeffrey S; Regal, Jean F

    2013-11-01

    Preeclampsia is a major obstetric problem defined by new-onset hypertension and proteinuria associated with compromised placental perfusion. Although activation of the complement system is increased in preeclampsia compared to normal pregnancy, it remains unclear whether excess complement activation is a cause or consequence of placental ischemia. Therefore, we hypothesized that complement activation is critical for placental ischemia-induced hypertension. We employed the reduced utero-placental perfusion pressure (RUPP) model of placental ischemia in the rat to induce hypertension in the third trimester and evaluated the effect of inhibiting complement activation with a soluble recombinant form of an endogenous complement regulator, human complement receptor 1 (sCR1; CDX-1135). On day 14 of a 21-day gestation, rats received either RUPP or Sham surgery and 15 mg/kg/day sCR1 or saline intravenously on days 14-18. Circulating complement component 3 decreased and complement activation product C3a increased in RUPP vs. Sham (p<0.05), indicating complement activation had occurred. Mean arterial pressure (MAP) measured on day 19 increased in RUPP vs. Sham rats (109.8±2.8 mmHg vs. 93.6±1.6 mmHg). Treatment with sCR1 significantly reduced elevated MAP in RUPP rats (98.4±3.6 mmHg, p<0.05) and reduced C3a production. Vascular endothelial growth factor (VEGF) decreased in RUPP compared to Sham rats, and the decrease in VEGF was not affected by sCR1 treatment. Thus, these studies have identified a mechanistic link between complement activation and the pregnancy complication of hypertension apart from free plasma VEGF and have identified complement inhibition as a potential treatment strategy for placental ischemia-induced hypertension in preeclampsia. PMID:23685261

  15. ?1-Adrenergic blockers exert antioxidant effects, reduce matrix metalloproteinase activity, and improve renovascular hypertension-induced cardiac hypertrophy.

    PubMed

    Rizzi, Elen; Guimaraes, Danielle A; Ceron, Carla S; Prado, Cibele M; Pinheiro, Lucas C; Martins-Oliveira, Alisson; Gerlach, Raquel F; Tanus-Santos, Jose E

    2014-08-01

    Hypertension induces left-ventricular hypertrophy (LVH) by mechanisms involving oxidative stress and unbalanced cardiac matrix metalloproteinase (MMP) activity. We hypothesized that ?1-adrenergic receptor blockers with antioxidant properties (nebivolol) could reverse hypertension-induced LVH more effectively than conventional ?1-blockers (metoprolol) when used at doses that exert similar antihypertensive effects. Two-kidney one-clip (2K1C) hypertension was induced in male Wistar rats. Six weeks after surgery, hypertensive and sham rats were treated with nebivolol (10 mg kg(-1)day(-1)) or metoprolol (20 mg kg(-1)day(-1)) for 4 weeks. Systolic blood pressure was monitored weekly by tail-cuff plethysmography. LV structural changes and fibrosis were studied in hematoxylin/eosin- and picrosirius-stained sections, respectively. Cardiac MMP levels and activity were determined by in situ zymography, gel zymography, and immunofluorescence. Dihydroethidium and lucigenin-derived chemiluminescence assays were used to assess cardiac reactive oxygen species (ROS) production. Nitrotyrosine levels were determined in LV samples by immunohistochemistry and green fluorescence and were evaluated using the ImageJ software. Cardiac protein kinase B/Akt (AKT) phosphorylation state was assessed by Western blot. Both ?-blockers exerted similar antihypertensive effects and attenuated hypertension-induced cardiac remodeling. Both drugs reduced myocyte hypertrophy and collagen deposition in 2K1C rats. These effects were associated with lower cardiac ROS and nitrotyrosine levels and attenuation of hypertension-induced increases in cardiac MMP-2 levels and in situ gelatinolytic activity after treatment with both ?-blockers. Whereas hypertension increased AKT phosphorylation, no effects were found with ?-blockers. In conclusion, we found evidence that two ?1-blockers with different properties attenuate hypertension-induced LV hypertrophy and cardiac collagen deposition in association with significant cardiac antioxidant effects and MMP-2 downregulation, thus suggesting a critical role for ?1-adrenergic receptors in mediating those effects. Nebivolol is not superior to metoprolol, at least with respect to their capacity to reverse hypertension-induced LVH. PMID:24933619

  16. 76 FR 76432 - Notice of Proposed Information for Public Comment for: Capture Energy Efficiency Measures for PIH

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-07

    ... URBAN DEVELOPMENT Notice of Proposed Information for Public Comment for: Capture Energy Efficiency... public comments on the subject proposal. HUD is creating the Capture Energy Efficiency Measures for PIH... lists the following information: Title of Proposal: Capture Energy Efficiency Measures for PIH...

  17. Reduced uterine perfusion pressure induces hypertension in the pregnant mouse

    PubMed Central

    Intapad, Suttira; Warrington, Junie P.; Spradley, Frank T.; Palei, Ana C.; Drummond, Heather A.; Ryan, Michael J.; Granger, Joey P.

    2014-01-01

    Despite preeclampsia being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for its pathogenesis have yet to be fully elucidated. Growing evidence indicates that reduced uteroplacental perfusion and the resulting placental ischemia triggers the cascade of events leading to this maternal disorder. While the well-established rat model of reduced uterine perfusion pressure (RUPP) is providing invaluable insight into the etiology of preeclampsia, the aim of this study was to develop a mouse model of reduced uterine perfusion to expand mechanistic investigation by incorporation with novel gene-targeted mice. To accomplish this aim, a sham surgical procedure or a restriction of blood flow at the abdominal aorta and the ovarian arteries was initiated at day 13 of gestation in C57BL/6J mice. Mean arterial pressure measured in conscious, chronically instrumented mice was significantly elevated in the RUPP (120 ± 4 mmHg) compared with the sham (104 ± 4 mmHg) mice at day 18 of gestation (P < 0.01). Placental ischemia reduced fetal weights (0.95 ± 0.04 and 0.80 ± 0.02 g; RUPP vs. Sham, respectively; P < 0.02) and increased circulating levels of antiangiogenic soluble fms-related tyrosine kinases (sFlt)-1 (P < 0.05) in the RUPP at day 18 of gestation. Plasma concentrations of sFlt-1 are increased in preeclamptic patients and in response to reduced uterine perfusion in the rat. Thus, these results suggest that the mouse model of reduced uterine perfusion is applicable to facilitate novel mechanistic investigation into the etiology of hypertension that results from placental ischemia during pregnancy. PMID:25298513

  18. Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension.

    PubMed

    Chirinos, Julio A; Segers, Patrick; Raina, Amresh; Saif, Hassam; Swillens, Abigail; Gupta, Amit K; Townsend, Raymond; Emmi, Anthony G; Kirkpatrick, James N; Keane, Martin G; Ferrari, Victor A; Wiegers, Susan E; St John Sutton, Martin G

    2010-02-01

    Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P < or = 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension. PMID:19966060

  19. Central overexpression of the TRH precursor gene induces hypertension in rats: antisense reversal.

    PubMed

    García, S I; Porto, P I; Alvarez, A L; Martinez, V N; Shaurli, D; Finkielman, S; Pirola, C J

    1997-09-01

    Extrahypothalamic TRH participates in cardiovascular regulation and spontaneous hypertension of the rat. To investigate whether an increase in central TRH activity produces hypertension we studied the effect of the preTRH overproduction induced by I.C.V. transfection with a naked eukaryotic expression plasmid vector which encodes preTRH (pCMV-TRH). Northern blot analysis and RT-PCR showed that pCMV-TRH was transcribed in vitro and in vivo. At 24, 48, and 72 hours, pCMV-TRH (100 microg) in a significant and dose-dependent manner increased 37%, 84%, and 49%, respectively, the diencephalic TRH content and SABP (42+/-3, 50+/-2, and 22+/-2 mm Hg, respectively) with respect to the vector without the preTRH cDNA insert (V[TRH(-)]) as measured by RIA and the plethysmographic method, respectively, in awake animals. In addition, using immunohistochemistry we found that the increase of TRH was produced in circumventricular areas where the tripeptide is normally located. To further analyze the specificity of these effects we studied the actions of 23-mer sense (S), antisense (AS), and 3'self-stabilized sense (Ss) and antisense (ASs) phosphorothioate oligonucleotides against the initiation codon region. Only ASs inhibited the increase of TRH content and SABP induced by pCMV-TRH treatment. In addition, pCMV-TRH-induced hypertension seems not to be mediated by central Ang II or serum TSH. To summarize, central TRH overproduction in periventricular areas induced by I.C.V. transfection produces hypertension in rats which is reversed by specific antisense treatment. This model may help in testing effective antisense oligodeoxynucleotides against other candidate genes. PMID:9323019

  20. Src Family Kinases (SFK) Mediate Angiotensin II-Induced Myosin Light Chain Phosphorylation and Hypertension

    PubMed Central

    Qin, Bo; Zhou, Junlan

    2015-01-01

    Angiotensin (Ang) II is the major bioactive peptide of the renin–angiotensin system (RAS); it contributes to the pathogenesis of hypertension by inducing vascular contraction and adverse remodeling, thus elevated peripheral resistance. Ang II also activates Src family kinases (SFK) in the vascular system, which has been implicated in cell proliferation and migration. However, the role of SFK in Ang II-induced hypertension is largely unknown. In this study, we found that administration of a SFK inhibitor SU6656 markedly lowered the level of systemic BP in Ang II-treated mice, which was associated with an attenuated phosphorylation of the smooth-muscle myosin-light-chain (MLC) in the mesenteric resistant arteries. In the cultured human coronary artery smooth muscle cells (SMCs), pretreatment with SU6656 blocked Ang II-induced MLC phosphorylation and contraction. These results for the first time demonstrate that SFK directly regulate vascular contractile machinery to influence BP. Thus our study provides an additional mechanistic link between Ang II and vasoconstriction via SFK-enhanced MLC phosphorylation in SMCs, and suggests that targeted inhibition of Src may provide a new therapeutic opportunity in the treatment of hypertension. PMID:26011449

  1. Experimental TIPS with spiral Z-stents in swine with and without induced portal hypertension

    SciTech Connect

    Kichikawa, Kimihiko; Saxon, Richard R.; Nishimine, Kiyoshi; Nishida, Norifumi; Uchida, Barry T.

    1997-05-15

    Purpose. To assess the suitability of spiral Z-stents for transjugular intrahepatic portosystemic shunt (TIPS) and the influence of portal hypertension on shunt patency in young swine. Methods. TIPS were established using spiral Z-stents in 14 domestic swine. In 7 animals, the portal venous pressure was normal; in the other 7, acute portal hypertension was induced by embolization of portal vein branches. Follow-up portal venography and histologic evaluations were done from 1 hr to 12 weeks after TIPS. Results. Follow-up transhepatic portal venograms showed progressive narrowing of the shunt, most priminent in the midportion of the tract. Ingrowth of liver parenchyma between the stent wires found after 3 weeks led to progressive shunt narrowing and shunt occlusion by 12 weeks. A pseudointima grew rapidly inside the stent, peaked in thickness around 4 weeks, and decreased later. Acutely created portal hypertension rapidly returned to normal and there was no difference in TIPS patency between the two groups of animals. Conclusion. Although the spiral Z-stent can be used as a device for creation of TIPS in patients with cirrhotic livers, it is associated with extensive liver ingrowth in swine that leads to rapid shunt occlusion. Portal hypertension was only transient in this model.

  2. Effect of magnesium supplementation on blood pressure and vascular reactivity in nitric oxide synthase inhibition-induced hypertension model.

    PubMed

    Basral?, Filiz; Koçer, Günnur; Ülker Karadamar, P?nar; Nas?rc?lar Ülker, Seher; Sat?, Leyla; Özen, Nur; Özyurt, Dilek; ?entürk, Ümit Kemal

    2015-12-01

    The aim of this study was to assess the effect of oral magnesium supplementation (Mg-supp) on blood pressure (BP) and possible mechanism in nitric oxide synthase (NOS) inhibition-induced hypertension model. Hypertension and/or Mg-supp were created by N-nitro-l-arginine methyl ester (25?mg/kg/day by drinking water) and magnesium-oxide (0.8% by diet) for 6 weeks. Systolic BP was measured weekly by tail-cuff method. The effects of hypertension and/or Mg-supp in thoracic aorta and third branch of mesenteric artery constriction and relaxation responses were evaluated. NOS-inhibition produced a gradually developing hypertension and the magnitude of the BP was significantly attenuated after five weeks of Mg-supp. The increased phenylephrine-induced contractile and decreased acetylcholine (ACh)-induced dilation responses were found in both artery segments of hypertensive groups. Mg-supp was restored ACh-relaxation response in both arterial segments and also Phe-constriction response in thoracic aorta but not in mesenteric arteries. The contributions of NO, prostaglandins and K(+) channels to the dilator response of ACh were similar in the aorta of all the groups. The contribution of the NO to the ACh-mediated relaxation response of mesenteric arteries was suppressed in hypertensive rats, whereas this was corrected by Mg-supp. The flow-mediated dilation response of mesenteric arteries in hypertensive rats failed and could not be corrected by Mg-supp. Whereas, vascular eNOS protein and magnesium levels were not changed and plasma nitrite levels were reduced in hypertensive rats. The results of this study showed that Mg-supp lowered the arterial BP in NOS-inhibition induced hypertension model by restoring the agonist-induced relaxation response of the arteries. PMID:26114348

  3. Laser-Induced Mouse Model of Chronic Ocular Hypertension

    E-print Network

    Sakaguchi, Donald S.

    an inducible mouse model of glaucoma. METHODS. An obstruction of aqueous humor outflow in adult C57BL6/J mice. 2003;44:4337­4346) DOI: 10.1167/iovs.03-0015 Glaucoma is a progressive optic neuropathy with charac and modifying glaucoma have not been clearly defined.4 Different molecular mediators have been proposed

  4. http://pih.sagepub.com/ Engineers, Part H: Journal of Engineering in

    E-print Network

    Martin, Ralph R.

    of active contraction. Skeletal muscle plays an important role in the human body system and function Parametric study of a Hill-type hyperelastic skeletal muscle model Published by: http, 2012pih.sagepub.comDownloaded from #12;437 Parametric study of a Hill-type hyperelastic skeletal muscle

  5. Evaluation of the Persistent Issues in History Laboratory for Virtual Field Experience (PIH-LVFE)

    ERIC Educational Resources Information Center

    Brush, Thomas; Saye, John; Kale, Ugur; Hur, Jung Won; Kohlmeier, Jada; Yerasimou, Theano; Guo, Lijiang; Symonette, Simone

    2009-01-01

    The Persistent Issues in History Laboratory for Virtual Field Experience (PIH-LVFE) combines a database of video cases of authentic classroom practices with multiple resources and tools to enable pre-service social studies teachers to virtually observe teachers implementing problem-based learning activities. In this paper, we present the results…

  6. Interleukin-6 Underlies Angiotensin II-induced Hypertension and Chronic Renal Damage

    PubMed Central

    Zhang, Weiru; Wang, Wei; Yu, Hong; Zhang, Yujin; Dai, Yingbo; Ning, Chen; Tao, Lijian; Sun, Hong; Kellems, Rodney E.; Blackburn, Michael R.; Xia, Yang

    2012-01-01

    Chronic kidney disease (CKD) is a prevalent life-threatening disease frequently associated with hypertension, progression to renal fibrosis and eventual renal failure. While the pathogenesis of CKD remains largely unknown, an increased inflammatory response is known to be associated with the disease and has long been speculated to contribute to disease development. However, the causative factors, the exact role of the increased inflammatory cascade in CKD and the underlying mechanisms for its progression remain unidentified. Here we report that interleukin-6 (IL-6) expression levels were significantly increased in the kidneys collected from CKD patients and further elevated in CKD patients characterized with hypertension. Functionally, we determined that angiotensin II (Ang II) is a causative factor responsible for IL-6 induction in the mouse kidney and that genetic deletion of IL-6 significantly reduced hypertension and key features of CKD including renal injury and progression to renal fibrosis in Ang II-infused mice. Mechanistically, we provide both human and mouse evidence that IL-6 is a key cytokine functioning downstream of Ang II signaling to directly induce fibrotic gene expression and preproendothelin-1 (prepro-ET-1) mRNA expression in the kidney. Overall, both the mouse and human studies reported here provide evidence that Ang II induces IL-6 production in the kidney and that, in addition to its role in hypertension, increased IL-6 may play an important pathogenic role in CKD by inducing fibrotic gene expression and ET-1 gene expression. These findings immediately suggest the IL-6 signaling is a novel therapeutic target to manage this devastating disorder affecting millions worldwide. PMID:22068875

  7. Interleukin 6 underlies angiotensin II-induced hypertension and chronic renal damage.

    PubMed

    Zhang, Weiru; Wang, Wei; Yu, Hong; Zhang, Yujin; Dai, Yingbo; Ning, Chen; Tao, Lijian; Sun, Hong; Kellems, Rodney E; Blackburn, Michael R; Xia, Yang

    2012-01-01

    Chronic kidney disease (CKD) is a prevalent life-threatening disease frequently associated with hypertension, progression to renal fibrosis, and eventual renal failure. Although the pathogenesis of CKD remains largely unknown, an increased inflammatory response is known to be associated with the disease and has long been speculated to contribute to disease development. However, the causative factors, the exact role of the increased inflammatory cascade in CKD, and the underlying mechanisms for its progression remain unidentified. Here we report that interleukin 6 (IL-6) expression levels were significantly increased in the kidneys collected from CKD patients and further elevated in CKD patients characterized with hypertension. Functionally, we determined that angiotensin II is a causative factor responsible for IL-6 induction in the mouse kidney and that genetic deletion of IL-6 significantly reduced hypertension and key features of CKD, including renal injury and progression to renal fibrosis in angiotensin II-infused mice. Mechanistically, we provide both human and mouse evidence that IL-6 is a key cytokine functioning downstream of angiotensin II signaling to directly induce fibrotic gene expression and preproendothelin 1 mRNA expression in the kidney. Overall, both the mouse and human studies reported here provide evidence that angiotensin II induces IL-6 production in the kidney, and that, in addition to its role in hypertension, increased IL-6 may play an important pathogenic role in CKD by inducing fibrotic gene expression and ET-1 gene expression. These findings immediately suggest that the IL-6 signaling is a novel therapeutic target to manage this devastating disorder affecting millions worldwide. PMID:22068875

  8. Tetrahydrocurcumin Protects against Cadmium-Induced Hypertension, Raised Arterial Stiffness and Vascular Remodeling in Mice

    PubMed Central

    Sangartit, Weerapon; Kukongviriyapan, Upa; Donpunha, Wanida; Pakdeechote, Poungrat; Kukongviriyapan, Veerapol; Surawattanawan, Praphassorn; Greenwald, Stephen E.

    2014-01-01

    Background Cadmium (Cd) is a nonessential heavy metal, causing oxidative damage to various tissues and associated with hypertension. Tetrahydrocurcumin (THU), a major metabolite of curcumin, has been demonstrated to be an antioxidant, anti-diabetic, anti-hypertensive and anti-inflammatory agent. In this study, we investigated the protective effect of THU against Cd-induced hypertension, raised arterial stiffness and vascular remodeling in mice. Methods Male ICR mice received CdCl2 (100 mg/l) via drinking water for 8 weeks. THU was administered intragastrically at dose of 50 or 100 mg/kg/day concurrently with Cd treatment. Results Administration of CdCl2 significantly increased arterial blood pressure, blunted vascular responses to vasoactive agents, increased aortic stiffness, and induced hypertrophic aortic wall remodeling by increasing number of smooth muscle cells and collagen deposition, decreasing elastin, and increasing matrix metalloproteinase (MMP)-2 and MMP-9 levels in the aortic medial wall. Supplementation with THU significantly decreased blood pressure, improved vascular responsiveness, and reversed the structural and mechanical alterations of the aortas, including collagen and elastin deposition. The reduction on the adverse response of Cd treatment was associated with upregulated eNOS and downregulated iNOS protein expressions, increased nitrate/nitrite level, alleviated oxidative stress and enhanced antioxidant glutathione. Moreover, THU also reduced the accumulation of Cd in the blood and tissues. Conclusions Our results suggest that THU ameliorates cadmium-induced hypertension, vascular dysfunction, and arterial stiffness in mice through enhancing NO bioavailability, attenuating oxidative stress, improving vascular remodeling and decreasing Cd accumulation in other tissues. THU has a beneficial effect in moderating the vascular alterations associated with Cd exposure. PMID:25502771

  9. Elevated Endothelial Hypoxia-Inducible Factor-1? Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

    PubMed

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2015-07-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1? (HIF-1?) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1? and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1? is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1? gene expression was induced by angiotensin II in a nuclear factor-?B-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1? and Nf-?b genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1? gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. PMID:25987665

  10. Growth hormone secretagogue receptor deficiency in mice protects against obesity?induced hypertension

    PubMed Central

    Harris, Louise E.; Morgan, David G.; Balthasar, Nina

    2014-01-01

    Abstract Growth hormone secretagogue receptor (GHS?R) signaling has been associated with growth hormone release, increases in food intake and pleiotropic cardiovascular effects. Recent data demonstrated that acute GHS?R antagonism leads to increases in mean arterial pressure mediated by the sympathetic nervous system in rats; a highly undesirable effect if GHS?R antagonism was to be used as a therapeutic approach to reducing food intake in an already obese, hypertensive patient population. However, our data in conscious, freely moving GHS?R deficient mice demonstrate that chronic absence of GHS?R signaling is protective against obesity?induced hypertension. GHS?R deficiency leads to reduced systolic blood pressure variability (SBPV); in response to acute high?fat diet (HFD)?feeding, increases in the sympathetic control of SBPV are suppressed in GHS?R KO mice. Our data further suggest that GHS?R signaling dampens the immediate HFD?mediated increase in spontaneous baroreflex sensitivity. In diet?induced obesity, absence of GHS?R signaling leads to reductions in obesity?mediated hypertension and tachycardia. Collectively, our findings thus suggest that chronic blockade of GHS?R signaling may not result in adverse cardiovascular effects in obesity. PMID:24760503

  11. Pulmonary hypertension

    MedlinePLUS

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  12. Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats.

    PubMed

    Qiao, Yu-Feng; Guo, Wen-Juan; Li, Lu; Shao, Shan; Qiao, Xi; Shao, Jin-Jin; Zhang, Qiong; Li, Rong-Shan; Wang, Li-Hua

    2016-01-01

    The aim of the present study was to investigate the protective effects of melatonin (MLT) on hypertension-induced renal injury and identify its mechanism of action. Twenty-four healthy male Wistar rats were divided into a sham control group (n=8), which was subjected to sham operation and received vehicle treatment (physiological saline intraperitoneally at 0.1 ml/100 g), a vehicle group (n=8), which was subjected to occlusion of the left renal artery and vehicle treatment, and the MLT group (n=8), which was subjected to occlusion of the left renal artery and treated with MLT (10 mg/kg/day). Pathological features of the renal tissues were determined using hematoxylin and eosin staining and Masson staining. Urine protein, serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical analysis was performed to determine the expression of heme oxygenase?1 (HO?1), intercellular adhesion molecule?1 (ICAM?1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, reverse transcription polymerase chain reaction was conducted to determine the mRNA expression of HO?1, ICAM?1, eNOS and iNOS. A marked decrease in blood pressure was noticed in the MLT group at week 4 compared with that of the vehicle group (P<0.01). Furthermore, MLT treatment attenuated the infiltration of inflammatory cells and oedema/atrophy of renal tubules. MLT attenuated hypertension-induced increases in urine protein excretion, serum creatinine and MDA as well as decreases in SOD activity in renal tissues. Furthermore, MLT attenuated hypertension-induced increases in iNOS and ICAM?1 as well as decreases in eNOS and HO?1 expression at the mRNA and protein level. In conclusion, the results of the present study indicated that MLT had protective roles in hypertension?induced renal injury. Its mechanism of action is, at least in part, associated with the inhibition of oxidative stress. PMID:26531807

  13. Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats

    PubMed Central

    QIAO, YU-FENG; GUO, WEN-JUAN; LI, LU; SHAO, SHAN; QIAO, XI; SHAO, JIN-JIN; ZHANG, QIONG; LI, RONG-SHAN; WANG, LI-HUA

    2016-01-01

    The aim of the present study was to investigate the protective effects of melatonin (MLT) on hypertension-induced renal injury and identify its mechanism of action. Twenty-four healthy male Wistar rats were divided into a sham control group (n=8), which was subjected to sham operation and received vehicle treatment (physiological saline intraperitoneally at 0.1 ml/100 g), a vehicle group (n=8), which was subjected to occlusion of the left renal artery and vehicle treatment, and the MLT group (n=8), which was subjected to occlusion of the left renal artery and treated with MLT (10 mg/kg/day). Pathological features of the renal tissues were determined using hematoxylin and eosin staining and Masson staining. Urine protein, serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical analysis was performed to determine the expression of heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, reverse transcription polymerase chain reaction was conducted to determine the mRNA expression of HO-1, ICAM-1, eNOS and iNOS. A marked decrease in blood pressure was noticed in the MLT group at week 4 compared with that of the vehicle group (P<0.01). Furthermore, MLT treatment attenuated the infiltration of inflammatory cells and oedema/atrophy of renal tubules. MLT attenuated hypertension-induced increases in urine protein excretion, serum creatinine and MDA as well as decreases in SOD activity in renal tissues. Furthermore, MLT attenuated hypertension-induced increases in iNOS and ICAM-1 as well as decreases in eNOS and HO-1 expression at the mRNA and protein level. In conclusion, the results of the present study indicated that MLT had protective roles in hypertension-induced renal injury. Its mechanism of action is, at least in part, associated with the inhibition of oxidative stress. PMID:26531807

  14. Depressor effect of chymase inhibitor in mice with high salt-induced moderate hypertension.

    PubMed

    Devarajan, Sankar; Yahiro, Eiji; Uehara, Yoshinari; Habe, Shigehisa; Nishiyama, Akira; Miura, Shin-Ichiro; Saku, Keijiro; Urata, Hidenori

    2015-12-01

    The aim of the present study was to determine whether long-term high salt intake in the drinking water induces hypertension in wild-type (WT) mice and whether a chymase inhibitor or other antihypertensive drugs could reverse the increase of blood pressure. Eight-week-old male WT mice were supplied with drinking water containing 2% salt for 12 wk (high-salt group) or high-salt drinking water plus an oral chymase inhibitor (TPC-806) at four different doses (25, 50, 75, or 100 mg/kg), captopril (75 mg/kg), losartan (100 mg/kg), hydrochlorothiazide (3 mg/kg), eplerenone (200 mg/kg), or amlodipine (6 mg/kg). Control groups were given normal water with or without the chymase inhibitor. Blood pressure and heart rate gradually showed a significant increase in the high-salt group, whereas a dose-dependent depressor effect of the chymase inhibitor was observed. There was also partial improvement of hypertension in the losartan- and eplerenone-treated groups but not in the captopril-, hydrochlorothiazide-, and amlodipine-treated groups. A high salt load significantly increased chymase-dependent ANG II-forming activity in the alimentary tract. In addition, the relative contribution of chymase to ANG II formation, but not actual average activity, showed a significant increase in skin and skeletal muscle, whereas angiotensin-converting enzyme-dependent ANG II-forming activity and its relative contribution were reduced by high salt intake. Plasma and urinary renin-angiotensin system components were significantly increased in the high-salt group but were significantly suppressed in the chymase inhibitor-treated group. In conclusion, 2% salt water drinking for 12 wk caused moderate hypertension and activated the renin-angiotensin system in WT mice. A chymase inhibitor suppressed both the elevation of blood pressure and heart rate, indicating a definite involvement of chymase in salt-sensitive hypertension. PMID:26432844

  15. Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats.

    PubMed

    Mohammadi, Sadollah; Najafi, Moslem; Hamzeiy, Hossein; Maleki-Dizaji, Nasrin; Pezeshkian, Masoud; Sadeghi-Bazargani, Homayon; Darabi, Masoud; Mostafalou, Sara; Bohlooli, Shahab; Garjani, Alireza

    2012-01-01

    Methylsulfonylmethane (MSM) is naturally occurring organic sulfur that is known as a potent antioxidant/anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on hemodynamics functions and oxidative stress in rats with monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Wistar rats were randomly assigned to 38-days treatment. MSM was administered to rats at 100, 200, and 400?mg/kg/day doses 10 days before a single dose of 60?mg/kg, IP, MCT. Hemodynamics of ventricles were determined by Powerlab AD instrument. Blood samples were obtained to evaluate changes in the antioxidative system including activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) and malondialdehyde (MDA). Improvements in cardiopulmonary hemodynamics were observed in the MSM-treated pulmonary arterial hypertensive rats, with a significant reduction in right ventricular systolic pressure (RSVP) and an increase in the mean arterial pressure (MAP). The values of CAT, SOD, GSH-px activities, and GSH were significantly lower in MCT-induced PAH (P < 0.01), but they were recovered to control levels of MSM-treated groups. Our present results suggest that long-term administration of the MSM attenuates MCT-induced PAH in rats through modulation of oxidative stress and antioxidant defense. PMID:23118745

  16. Protective Effects of Methylsulfonylmethane on Hemodynamics and Oxidative Stress in Monocrotaline-Induced Pulmonary Hypertensive Rats

    PubMed Central

    Mohammadi, Sadollah; Najafi, Moslem; Hamzeiy, Hossein; Maleki-Dizaji, Nasrin; Pezeshkian, Masoud; Sadeghi-Bazargani, Homayon; Darabi, Masoud; Mostafalou, Sara; Bohlooli, Shahab; Garjani, Alireza

    2012-01-01

    Methylsulfonylmethane (MSM) is naturally occurring organic sulfur that is known as a potent antioxidant/anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on hemodynamics functions and oxidative stress in rats with monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Wistar rats were randomly assigned to 38-days treatment. MSM was administered to rats at 100, 200, and 400?mg/kg/day doses 10 days before a single dose of 60?mg/kg, IP, MCT. Hemodynamics of ventricles were determined by Powerlab AD instrument. Blood samples were obtained to evaluate changes in the antioxidative system including activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) and malondialdehyde (MDA). Improvements in cardiopulmonary hemodynamics were observed in the MSM-treated pulmonary arterial hypertensive rats, with a significant reduction in right ventricular systolic pressure (RSVP) and an increase in the mean arterial pressure (MAP). The values of CAT, SOD, GSH-px activities, and GSH were significantly lower in MCT-induced PAH (P < 0.01), but they were recovered to control levels of MSM-treated groups. Our present results suggest that long-term administration of the MSM attenuates MCT-induced PAH in rats through modulation of oxidative stress and antioxidant defense. PMID:23118745

  17. Treatment of sunitinib-induced hypertension in solid tumor by nitric oxide donors?

    PubMed Central

    León-Mateos, L.; Mosquera, J.; Antón Aparicio, L.

    2015-01-01

    Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are overexpressed in the majority of renal cell carcinomas. This characteristic has supported the rationale of targeting VEGF-driven tumour vascularization, especially in clear cell RCC. VEGF-inhibiting strategies include the use of tyrosine kinase inhibitors (sunitinib, axitinib, pazopanib, and sorafenib) and neutralizing antibodies such as bevacizumab. Hypertension (HTN) is one of the most common adverse effects of angiogenesis inhibitors. HTN observed in clinical trials appears to correlate with the potency of VEGF kinase inhibitor against VEGFR-2: agents with higher potency are associated with a higher incidence of HTN. Although the exact mechanism by tyrosine kinase inhibitors induce HTN has not yet been completely clarified, two key hypotheses have been postulated. First, some studies have pointed to a VEGF inhibitors-induced decrease in nitric oxide synthase (NOS) and nitric oxide (NO) production, that can result in vasoconstriction and increased blood pressure. VEGF, mediated by PI3K/Akt and MAPK pathway, upregulates the endothelial nitric oxide synthase enzyme leading to up-regulation of NO production. So inhibition of signaling through the VEGF pathway would lead to a decrease in NO production, resulting in an increase in vascular resistance and blood pressure. Secondly a decrease in the number of microvascular endothelial cells and subsequent depletion of normal microvessel density (rarefaction) occurs upon VEGF signaling inhibition. NO donors could be successfully used not only for the treatment of developed angiogenesis-inhibitor-induced hypertension but also for preventive effects. PMID:26386874

  18. A case of mild ocular manifestations in pregnancy induced hypertension with HELLP syndrome.

    PubMed

    Wenzel, M; Lehnen, H

    1994-06-01

    There is a correlation between the degree of retinal changes and the severity of pregnancy induced hypertension. This correlation does not hold true for a subgroup of these patients with hemolysis, elevated liver enzymes and a low platelet count. This array of findings has been termed HELLP syndrome by Weinstein (1982) and may be present although the clinical picture of severe preeclampsia is absent. Pregnancies complicated by HELLP syndrome are associated with poor maternal and fetal outcome. We report a case in which minor ocular signs led to the diagnosis of a HELLP syndrome. Ophthalmologists should be aware of this rare complication of pregnancy. PMID:7976276

  19. Diesel exhaust induced pulmonary and cardiovascular impairment: The role of hypertension intervention

    SciTech Connect

    Kodavanti, Urmila P.; Thomas, Ronald F.; Ledbetter, Allen D.; Schladweiler, Mette C.; Bass, Virginia; Krantz, Q. Todd; King, Charly; Nyska, Abraham; Richards, Judy E.; Andrews, Debora; Gilmour, M. Ian

    2013-04-15

    Exposure to diesel exhaust (DE) and associated gases is linked to cardiovascular impairments; however, the susceptibility of hypertensive individuals is poorly understood. The objectives of this study were (1) to determine cardiopulmonary effects of gas-phase versus whole-DE and (2) to examine the contribution of systemic hypertension in pulmonary and cardiovascular effects. Male Wistar Kyoto (WKY) rats were treated with hydralazine to reduce blood pressure (BP) or L-NAME to increase BP. Spontaneously hypertensive (SH) rats were treated with hydralazine to reduce BP. Control and drug-pretreated rats were exposed to air, particle-filtered exhaust (gas), or whole DE (1500 ?g/m{sup 3}), 4 h/day for 2 days or 5 days/week for 4 weeks. Acute and 4-week gas and DE exposures increased neutrophils and ?-glutamyl transferase (?-GT) activity in lavage fluid of WKY and SH rats. DE (4 weeks) caused pulmonary albumin leakage and inflammation in SH rats. Two-day DE increased serum fatty acid binding protein-3 (FABP-3) in WKY. Marked increases occurred in aortic mRNA after 4-week DE in SH (eNOS, TF, tPA, TNF-?, MMP-2, RAGE, and HMGB-1). Hydralazine decreased BP in SH while L-NAME tended to increase BP in WKY; however, neither changed inflammation nor BALF ?-GT. DE-induced and baseline BALF albumin leakage was reduced by hydralazine in SH rats and increased by L-NAME in WKY rats. Hydralazine pretreatment reversed DE-induced TF, tPA, TNF-?, and MMP-2 expression but not eNOS, RAGE, and HMGB-1. ET-1 was decreased by HYD. In conclusion, antihypertensive drug treatment reduces gas and DE-induced pulmonary protein leakage and expression of vascular atherogenic markers. - Highlights: ? Acute diesel exhaust exposure induces pulmonary inflammation in healthy rats. ? In hypertensive rats diesel exhaust effects are seen only after long term exposure. ? Normalizing blood pressure reverses lung protein leakage caused by diesel exhaust. ? Normalizing blood pressure reverses atherogenic effects of diesel exhaust. ? Diesel exhaust and hydralazine cause similar aorta effect on vascular tone markers.

  20. 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension

    PubMed Central

    Ding, Yan; Wu, Cheng-Chia; Garcia, Victor; Dimitrova, Irina; Weidenhammer, Adam; Joseph, Gregory; Zhang, Frank; Manthati, Vijay L.; Falck, John R.; Capdevila, Jorge H.

    2013-01-01

    20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented 5?-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14?/? mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 ?m) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12–20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 ?m; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. PMID:23825080

  1. Visualizing oxidative stress-induced depression of cardiac vagal baroreflex by MRI/DTI in a mouse neurogenic hypertension model.

    PubMed

    Tsai, Ching-Yi; Su, Chia-Hao; Baudrie, Véronique; Laude, Dominique; Weng, Jun-Cheng; Chang, Alice Y W; Chan, Julie Y H; Elghozi, Jean-Luc; Chan, Samuel H H

    2013-11-15

    A clinical hallmark of hypertension is impairment of the cardiac vagal baroreflex, which maintains stable blood pressure and heart rate under physiological conditions. There is also evidence that oxidative stress in the brain is associated with neurogenic hypertension. We tested the hypothesis that an augmented superoxide level in the nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents, contributes to the depression of cardiac vagal baroreflex by disrupting the connectivity between the NTS and the nucleus ambiguus (NA), the origin of the vagus nerve, during neurogenic hypertension. An experimental model of neurogenic hypertension that employed intracerebroventricular infusion of angiotensin II in male adult C57BL/6 mice was used. Based on tractographic evaluations using magnetic resonance imaging/diffusion tensor imaging of the medulla oblongata in the brain stem, we found that the connectivity between the NTS and NA was disrupted in neurogenic hypertension, concurrent with impairment of the cardiac vagal baroreflex as detected by radiotelemetry. We further found that the disrupted NTS-NA connectivity was reversible, and was related to oxidative stress induced by augmented levels of NADPH oxidase-generated superoxide in the NTS. We conclude that depression of the cardiac vagal baroreflex induced by oxidative stress in the NTS in the context of neurogenic hypertension may be manifested in the form of dynamic alterations in the connectivity between the NTS and NA. PMID:23747290

  2. Endothelin-1 is not a Mechanism of IL-17 Induced Hypertension during Pregnancy

    PubMed Central

    Cornelius, Denise C; Wallace, Kedra; Kiprono, Luissa; Dhillon, Pushpinder; Moseley, Janae; LaMarca, Babbette

    2014-01-01

    Preeclampsia is characterized as new onset maternal hypertension and proteinuria after 20 weeks gestation. Studies suggest that endothelin (ET-1) is a regulator of vascular function in preeclampsia and plays a major role in mediating chronic reduction in uterine perfusion pressure (RUPP)-induced hypertension. We recently demonstrated a role for the autoimmune cytokine interleukin 17 (IL-17) in causing placental oxidative stress and hypertension during pregnancy. In this current study, we investigated the role of ET-1 as a potential mechanism by which TH17 cells and IL-17 mediate hypertension in preeclampsia. While IL-17 infusion into normal pregnant rats increased blood pressure in a dose-responsive manner (98+/-2 mmHg in NP (n=20) to 105+/-3 mmHg in IL-17 (50pg/day, n=20) to 120+/-4 mmHg in IL-17 (100pg/day, n=10) to 123+/-3 mmHg in IL-17 (150 pg/day, n=7), it decreased local endothelin in placentas (NP (n=10) 7.5±0.3; IL-17 (100 pg/day, n=5) 6.4±0.2; IL-17 (150 pg/day, n=12) 4.5+1.5) and renal cortices (NP (n=8) 7.9 + 0.4; IL-17 (100 pg/day, n=6) 7.1±0.4; IL-17 (150 pg/day, n=4) 1.6 +0.7 during pregnancy. In addition, increasing IL-17 directly reduced secretion of ET-1 by human umbilical venous endothelial cells (HUVECs). HUVEC ET-1 secretion decreased from that seen in serum free media 42.7±7.7 pg/ml to 36.2 ± 5.9 pg/ml at 10 pg IL-17 to 31.3 ± 5.1 pg/ml at 10 ?g IL-17. Our observations suggest that IL-17 negatively regulates the ET-1 pathway in local tissues and cultured endothelial cells and that the ET-1 pathway is not a mechanism by which IL-17 causes hypertension during pregnancy. PMID:25414910

  3. Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension.

    PubMed

    Satwiko, Muhammad Gahan; Ikeda, Koji; Nakayama, Kazuhiko; Yagi, Keiko; Hocher, Berthold; Hirata, Ken-ichi; Emoto, Noriaki

    2015-09-25

    Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. PMID:26275708

  4. Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension

    SciTech Connect

    Catella, F.; Lawson, J.A.; Fitzgerald, D.J.; FitzGerald, G.A. )

    1990-08-01

    Arachidonic acid is metabolized by means of P450 isoenzyme(s) to form epoxyeicosatrienoic acids (EETs) and their corresponding dihydroxy derivatives (DHETs). In the present study, we established the presence in human urine of 8,9-, 11,12-, and 14,15-EETs and their corresponding DHETs by developing quantitative assays and using negative ion, chemical ionization GC/MS and octadeuterated internal standards. Urinary excretion of 8,9- and 11,12-DHET increased in healthy pregnant women compared with nonpregnant female volunteers. By contrast, excretion of 11,12-DHET and 14,15-DHET, but not the 8,9-DHET regioisomer, increased even further in patients with pregnancy-induced hypertension. Intravenous administration of (3H)14,15-EET to three dogs markedly increased its DHET in plasma. The terminal half-life ranged from 7.9-12.3 min and the volume of distribution (3.5-5.3 liters) suggested limited distribution outside the plasma compartment. Negligible radioactivity was detected in urine; this fact infers that under physiological circumstances, urinary DHETs largely derive from the kidney. That P450 metabolites of arachidonic acid are formed in humans supports the hypothesis that these metabolites contribute to the physiological response to normal pregnancy and the pathophysiology of pregnancy-induced hypertension.

  5. [Role of renal sympathetic nerve and oxidative stress in foot shock-induced hypertension in rats].

    PubMed

    Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Dong, Tao; Zhang, Guo-Xing

    2015-06-25

    The present study was aimed to investigate the roles of renal sympathetic nerve and oxidative stress in the development of foot shock-induced hypertension. Ninety rats were divided into 6 groups (the number of each group was 15): control group, foot shock group, denervation of renal sympathetic nerve group, denervation of renal sympathetic nerve + foot shock group, Tempol treatment + foot shock group, denervation of renal sympathetic nerve + Tempol treatment + foot shock group. Rats were received electrical foot shock for 14 days (2-4 mA, 75 V, shocks of 50-100 ms every 30 s, for 4 h each session through an electrified grid floor every day). Renal sympathetic ablation was used to remove bilateral renal sympathetic nerve in rats (rats were allowed to recover for one week before the beginning of the foot shock procedure). The antioxidant Tempol was injected intraperitoneally at 1 h before foot shock. Systolic blood pressure was measured at 1 h after foot shock on day 0, 3, 7, 10 and 14. Contents of thiobarbituric acid reactive substance (TBARS), renin, angiotensin II (AngII) and glutathione peroxidase (GSH-Px) in plasma were measured by ELISA after 14-day foot shock. The results showed that systolic blood pressure of foot shock group was significantly increased (P < 0.05) compared with that of control group from day 7 to day 14 of foot shock. Denervation of renal sympathetic nerve and/or Tempol treatment significantly reduced the increase of systolic blood pressure induced by foot shock. Levels of TBARS, renin and AngII in plasma were increased significantly in foot shock group compared with that of control group (P < 0.05). Plasma GSH-Px concentration was decreased in foot shock group rats compared with that of control group (P < 0.05). Denervation of renal sympathetic nerve and/or tempol treatment significantly reduced the increase in TBARS, renin, AngII levels induced by foot shock in comparison with that of foot shock group (P < 0.05), but had no effects on the reduction of GSH-Px concentration. The results suggest that renal sympathetic nerve may play an important role in the development of foot shock-induced hypertension, and renal sympathetic nerve may influence oxidative stress and directly or indirectly activate renin-angiotensin-aldosterone system, so the foot shock-induced high blood pressure may be maintained and hypertension may therefore be produced. PMID:26109307

  6. Ocular Hypertension

    MedlinePLUS

    ... Eye Health News Consumer Alerts What Is Ocular Hypertension? Tweet Ocular hypertension is when the pressure inside the eye (intraocular ... IOP) is higher than normal. What Is Ocular Hypertension? Ocular Hypertension Causes Ocular Hypertension Symptoms Ocular Hypertension ...

  7. Is hypercalcemic diet a possible antidote to oral contraceptive-induced hypertension?

    PubMed

    Okwusidi, J I; Alabi, K I; Olatunji, L A; Oyesola, T O

    2010-01-01

    Administration of oral contraceptive (OC) has been associated with body fluid retention and in high doses over a long period, promotes hypertension. This present investigation tests the hypothesis that the dietary calcium supplementation increases salt and water excretion in OC (norgestre/ethinylestradiol) treated 32 female albino rats randomly distributed into four (1-4) groups of 8 rats each: Control, OC-treated, OC-treated+ Calcium diet fed and Calcium diet fed only respectively. OC was administered to the appropriate groups by gavage. Experimental diet contained 2.5% calcium supplement. Plasma and urinary [Na+] [K+] were evaluated after 8 weeks of experimentation by flame photometry and plasma [Ca2+] by colorimetric method. OC-treatment induced a significant fall in urinary [Na+]. Water excretion was significantly reduced in these animals (control, 3.1±0.56 Vs OC-treated rats, 1.47±0.16). OC-treated rats had significantly higher plasma [K+] compared to control rats. Calcium supplementation induced increases in plasma [Na+], [K+] and augmented urinary Na+ excretion (OC-treated + Ca2+ diet Vs OC-treated only). Compared with the control rats, high Ca2+ diet fed rats exhibited significant increases in plasma [Na+] and [K+] accompanied by significant decreases in urinary H20 excretion. These results strongly suggest that high dietary Ca2+ supplementation increases salt and water excretion in OC-treated rats and potentially moderates fluid retention and blood pressure in these animals, and may be of clinical significance in OC-induced abnormal fluid retention and perhaps OC-induced hypertension. PMID:22314948

  8. Oxidant and enzymatic antioxidant status (gene expression and activity) in the brain of chickens with cold-induced pulmonary hypertension.

    PubMed

    Hassanpour, Hossein; Khalaji-Pirbalouty, Valiallah; Nasiri, Leila; Mohebbi, Abdonnaser; Bahadoran, Shahab

    2015-11-01

    To evaluate oxidant and antioxidant status of the brain (hindbrain, midbrain, and forebrain) in chickens with cold-induced pulmonary hypertension, the measurements of lipid peroxidation, protein oxidation, antioxidant capacity, enzymatic activity, and gene expression (for catalase, glutathione peroxidase, and superoxide dismutases) were done. There were high lipid peroxidation/protein oxidation and low antioxidant capacity in the hindbrain of cold-induced pulmonary hypertensive chickens compared to control (P?hypertensive chickens, superoxide dismutase activity was decreased (forebrain, midbrain, and hindbrain), while catalase activity was increased (forebrain and midbrain) (P?induced pulmonary hypertensive chickens. Probably, these situations in the oxidant and antioxidant status of the brain especially hindbrain may change its function at cardiovascular center and sympathetic nervous system to exacerbate pulmonary hypertension. PMID:25939899

  9. New Insights on the Maternal Diet Induced-Hypertension: Potential Role of the Phenotypic Plasticity and Sympathetic-Respiratory Overactivity

    PubMed Central

    Costa-Silva, João H.; de Brito-Alves, José L.; Barros, Monique Assis de V.; Nogueira, Viviane Oliveira; Paulino-Silva, Kássya M.; de Oliveira-Lira, Allan; Nobre, Isabele G.; Fragoso, Jéssica; Leandro, Carol G.

    2015-01-01

    Systemic arterial hypertension (SAH) is an important risk factor for cardiovascular disease and affects worldwide population. Current environment including life style coupled with genetic programming have been attributed to the rising incidence of hypertension. Besides, environmental conditions during perinatal development such as maternal malnutrition can program changes in the integration among renal, neural, and endocrine system leading to hypertension. This phenomenon is termed phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental stimuli without genetic change, following a novel or unusual input during development. Human and animal studies indicate that fetal exposure to an adverse maternal environment may alter the renal morphology and physiology that contribute to the development of hypertension. Recently, it has been shown that the maternal protein restriction alter the central control of SAH by a mechanism that include respiratory dysfunction and enhanced sympathetic-respiratory coupling at early life, which may contribute to adult hypertension. This review will address the new insights on the maternal diet induced-hypertension that include the potential role of the phenotypic plasticity, specifically the perinatal protein malnutrition, and sympathetic-respiratory overactivity. PMID:26635631

  10. Inactivation of p53 Is Sufficient to Induce Development of Pulmonary Hypertension in Rats

    PubMed Central

    Jacquin, S.; Rincheval, V.; Mignotte, B.; Richard, S.; Humbert, M.; Mercier, O.; Londoño-Vallejo, A.; Fadel, E.; Eddahibi, S.

    2015-01-01

    Objective Pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterial hypertension (PAH) show similarities to cancer cells. Due to the growth-suppressive and pro-apoptotic effects of p53 and its inactivation in cancer, we hypothesized that the p53 pathway could be altered in PAH. We therefore explored the involvement of p53 in the monocrotaline (MCT) rat model of pulmonary hypertension (PH) and the pathophysiological consequences of p53 inactivation in response to animal treatment with pifithrin-? (PFT, an inhibitor of p53 activity). Methods and Results PH development was assessed by pulmonary arterial pressure, right ventricular hypertrophy and arterial wall thickness. The effect of MCT and PFT on lung p53 pathway expression was evaluated by western blot. Fourteen days of daily PFT treatment (2.2 mg/kg/day), similar to a single injection of MCT (60 mg/kg), induced PH and aggravated MCT-induced PH. In the first week after MCT administration and prior to PH development, p53, p21 and MDM2 protein levels were significantly reduced; whereas PFT administration effectively altered the protein level of p53 targets. Anti-apoptotic and pro-proliferative effects of PFT were revealed by TUNEL and MTT assays on cultured human PA-SMCs treated with 50 ?M PFT. Conclusions Pharmacological inactivation of p53 is sufficient to induce PH with a chronic treatment by PFT, an effect related to its anti-apoptotic and pro-proliferative properties. The p53 pathway was down-regulated during the first week in the rat MCT model. These in vivo experiments implicate the p53 pathway at the initiation stages of PH pathogenesis. PMID:26121334

  11. CYP450 4A Inhibition Attenuates O2 Induced Arteriolar Constriction in Chronic but not Acute Goldblatt Hypertension

    PubMed Central

    Kunert, Mary Pat; Friesma, Jill; Falck, John R.; Lombard, Julian H.

    2009-01-01

    We explored the role of 20-hydroxy-5Z, 8Z, 11Z, 14Z-eicosatetraenoic acid (20-HETE) in oxygen-induced vasoconstriction in a normal renin form of hypertension [the 1 kidney-1 clip Goldblatt hypertensive rat (1K1C)] and a high renin form of hypertension [the 2 kidney-1 clip Goldblatt hypertensive rat (2K1C)]. A silver clip was placed around the left renal artery of adult Sprague-Dawley males. The right kidney was removed in the 1K1C group and left intact in the 2K1C group. Arteriolar responses to elevation of O2 concentration in the superfusion solution from 0% O2 to 21% O2 were determined in the in situ cremaster muscle before and after inhibition of cytochrome P450 4A ?-hydroxylase (CYP450 4A) with N-methyl-sulfonyl-12, 12-dibromododec-11-enamide (DDMS). Arteriolar constriction to elevated PO2 was enhanced in the chronic 1K1C but not the acute 1K1C or 2K1C. DDMS eliminated O2-induced arteriolar constriction in the 9 week 1K1C, but had no effect in the 2 wk 1K1C, and only partially inhibited O2-induced constriction of arterioles in the 4 wk 2K1C rat. These findings indicate that although the CYP4A/20-HETE system contributes to arteriolar constriction in response to elevated PO2 in the established stage of 1K1C renovascular hypertension, physiological alterations in other mechanisms are the primary determinants of O2-induced constriction of arterioles in the early and developing stages of 1K1C and 2K1C hypertension. PMID:19761780

  12. Glucocorticoid-induced hypertension in rats: role of the central muscarinic cholinergic system.

    PubMed

    Torres, N; Fanelli, M; Alvarez, A L; Santajuliana, D; Finkielman, S; Pirola, C J

    1991-05-01

    Betamethasone was administered on alternate days to rats, and the role of the central cholinergic system in the development of hypertension assessed. After 15 days of treatment the systolic blood pressure of treated rats was significantly higher than that of control rats. Peripheral administration of atropine but not of methyl atropine reduced systolic pressure in glucocorticoid-treated rats and had no effect in controls. Therefore, [3H]quinuclidinyl benzylate binding, sodium-dependent high-affinity choline uptake and choline acetyltransferase studies were performed in the septal area, anteroventrolateral medulla (AVLM), anterior hypothalamic preoptic area (AH/PO) and hypothalamus. The density of muscarinic receptors was increased in the hypothalamus and AVLM of treated rats without significant changes in affinity. Choline acetyltransferase activity significantly decreased in the AVLM and increased in the AH/PO. In addition, a decrease in the hypothalamus and an increase in the AH/PO of sodium-dependent high-affinity choline uptake was observed in glucocorticoid-treated rats. These results suggest the presence of an enhanced muscarinic cholinergic activity in several brain nuclei in rats with glucocorticoid-induced hypertension. This activation could be due to pre- and post-synaptic hypersensitivity. PMID:2040860

  13. Comparison of foetomaternal circulation in normal pregnancies and pregnancy induced hypertension using color Doppler studies.

    PubMed

    Gupta, Shikha; Misra, R; Ghosh, U K; Gupta, V; Srivastava, D

    2014-01-01

    The aim of present study was to assess fetomaternal blood flows in normal and abnormal pregnancies using color Doppler indices. Subjects were divided into two groups as: Group A of 25 subjects of normal pregnancy as controls and group B of 25 subjects of pregnancy induced hypertension. All the subjects were lying in the age-group of 25-35 years and having 28 to 34 weeks of gestation; the patients were evaluated by detailed history and were subjected to complete general examination. Blood pressure was taken on two occasions at least 6 hours apart. Systemic examination and obstetrical examination was done in all subjects. All cases were subjected to pathological tests- Haemogram, Test for proteins in urine. Ultrasound assessment of fetal growth was done by measuring BPD (Biparietal diameter), HC (Head circumference), FL (Femur length) and AC (Abdominal circumference): Average gestational age and effective fetal weight was then calculated by ultrasound machine. Color Doppler was used to assess the various Doppler indices indices: Pulsatility index (PI), Resistive index (RI) and Systolic diastolic ratio (S/D ratio) in bilateral uterine, umbilical and middle cerebral arteries and compared to the standard normograms. Percentage of subjects having abnormal Doppler indices were calculated. Assessment of percentage of SGA (small for gestational age) fetuses was done in all the three groups. Decline in mean values of all Doppler indices was found with advancing gestational age in normal pregnancy suggesting decreased vascular resistance and increased blood flow in fetomaternal circulation. In pregnancy induced hypertensives, the mean values of Doppler indices showed a decline as in normal pregnancy but showed an increase (more than 2 S.D. of the mean) for that gestational age in comparison to the control group suggesting increased impedance to blood flow in uteroplacental and fetomaternal circulation. Umbilical artery Doppler indices were found to be the most sensitive indicator of uteroplacental and fetoplacental insufficiency in pregnancy induced hypertensives (P = 0.001). Thus we concluded that color Doppler can detect changes in fetomaternal circulation which correlate strongly with the fetal growth and therefore associated with pregnancy outcome. PMID:25906613

  14. Orexin A regulates cardiovascular responses in stress-induced hypertensive rats.

    PubMed

    Xiao, Fen; Jiang, Meiyan; Du, Dongshu; Xia, Chunmei; Wang, Jin; Cao, Yinxiang; Shen, Linlin; Zhu, Danian

    2013-04-01

    Several pieces of evidence indicate that the rostral ventrolateral medulla (RVLM) is probably one of the key neural structures mediating the pressor effects of orexins in the brain. Nitric oxide synthase/nitric oxide (NOS/NO) system in the RVLM modulates cardiovascular activities. Our experiments were designed to test the hypothesis that orexin-A (OXA) is involved in the mechanism of stress-induced hypertension (SIH) by adjusting NOS/NO system in the RVLM. The stress-induced hypertensive rats (SIHR) model was established by electric foot-shocks and noises. Here we examined the expression of OXA immunoreactive (OXA-IR) cells in the lateral hypothalamus (LH) and the protein level of orexin 1 receptor (OX1R) in the RVLM of SIHR, and we found that the expressions of OXA-IR and OX1R were higher than those of the control group. The double-staining immunohistochemical evidence showed that OX1R immunoreactive (OX1R-IR) cells and neuronal nitric oxide synthase (nNOS) or inducible nitric oxide synthase (iNOS) immunoreactive (IR) cells were co-localizated in the RVLM. Microinjection of OXA (10, 50, 100 pmol/100 nl) into the unilateral (right) RVLM of control rats or SIHR produced pressor and tachycardiac effects in a dose-dependent manner. SB-408124 (100 pmol/100 nl, an antagonist of OX1R) or TCS OX2 29 (100 pmol/100 nl, an antagonist of OX2R) partly abolished the cardiovascular effects of exogenously-administrated OXA into the RVLM of control rats and SIHR, and lowered the increased systolic blood pressure (SBP) and heart rate (HR) of SIHR, with no difference in statistical significance between the two antagonists' effects. Microinjection into the RVLM of both control and SIHR groups of 7-Ni (0.05 pmol/100 nl, nNOS inhibitor) or Methylene Blue [100 pmol/100 nl, an inhibitor of soluble guanylate cyclase (sGC)] suppressed the OXA-induced increase of SBP and HR, whereas microinjection of AG (1, 10, 100 pmol/100 nl) had no obvious effects on the OXA-induced increase of SBP and HR. Our results indicate that OXA in the RVLM may participate in the central regulation of cardiovascular activities in SIHR, and OX1R and OX2R both have important roles in it. The cardiovascular effects of OXA in the RVLM may be induced by nNOS-derived NO, which activated sGC-associated signaling pathway. PMID:23147417

  15. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    PubMed Central

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M), rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS), to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification. PMID:26696906

  16. Heme oxygenase induction attenuates TNF-?-induced hypertension in pregnant rodents

    PubMed Central

    George, Eric M.; Stout, Jacob M.; Stec, David E.; Granger, Joey P.

    2015-01-01

    Pre-eclampsia is a hypertensive disorder of pregnancy initiated by placental insufficiency and chronic ischemia. In response, several pathways activated in the placenta are responsible for the maternal syndrome, including increased production of the anti-angiogenic protein, sFlt-1, and inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-?). Previous studies have demonstrated that heme oxygenase (HO) induction can block TNF-? pathways in vitro and attenuate placental ischemia-induced sFlt-1 in vivo. Here, we investigated whether HO-1 induction could attenuate TNF-?-induced hypertension in pregnant rats. In response to TNF-? infusion (100 ng/day i.p.), maternal mean arterial pressure (MAP) increased vs. control animals (104 ± 3 vs. 119 ± 3 mmHg). HO-1 induction had no effect in control animals, but significantly decreased MAP in TNF-?-infused animals (108 ± 2 mmHg). Placental vascular endothelial growth factor (VEGF) was decreased in response to TNF-? infusion (92 ± 4 vs. 76 ± 2 pg/mg). Placental sFlt-1 was increased by TNF-? infusion (758 ± 45 vs. 936 ± 46 pg/mg, p < 0.05), which trended to normalization by HO-1 induction (779 ± 98 pg/mg). In contrast, HO-1 induction had no significant effect on placental VEGF in TNF-?-infused animals. Taken together, these data suggest that one of the key mechanisms by which HO exerts cytoprotective actions in the placenta during inflammation due to chronic ischemia is through suppression of sFlt-1. Further work elucidating the bioactive metabolites of HO-1 in innate inflammatory responses to placental ischemia is warranted. PMID:26347650

  17. CYP4A2-Induced Hypertension is 20-HETE and Angiotensin II-Dependent

    PubMed Central

    Sodhi, Komal; Wu, Cheng-Chia; Cheng, Jennifer; Gotlinger, Katherine; Inoue, Kazuyoshi; Goli, Mohan; Falck, John R.; Abraham, Nader G.; Schwartzman, Michal L.

    2010-01-01

    We have previously shown that increased vascular endothelial expression of CYP4A2 leads to 20-HETE-dependent hypertension. The renin-angiotensin system (RAS) is a key regulator of blood pressure. In this study, we examined possible interactions between 20-HETE and RAS. In normotensive (110±3 mmHg) Sprague Dawley rats transduced with a lentivirus expressing the CYP4A2 cDNA under the control of an endothelial-specific promoter (VECAD-4A2), systolic blood pressure increased rapidly, reaching 139±1, 145±3 and 150±2 mmHg at 3, 5 and 10 days after transduction; blood pressure remained elevated, thereafter, with maximum levels of 163±3 mmHg. Treatment with lisinopril, losartan or the 20-HETE antagonist 20-hydroxyeicosa-6(Z), 15(Z)-dienoic acid (20-HEDE) decreased blood pressure to control values, but blood pressure returned to its high levels after cessation of treatment. Endothelial-specific overexpression of CYP4A2 resulted in increased expression of vascular angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) and increased levels of plasma and tissue Angiotensin II; all were attenuated by treatment with HET0016, an inhibitor of 20-HETE synthesis, or with 20-HEDE. In cultured endothelial cells, 20-HETE specifically and potently induced ACE expression without altering the expression of ACE2, angiotensinogen or angiotensin II receptors. This is the first study to demonstrate that 20-HETE, a key constrictor eicosanoid in the microcirculation, induces ACE and AT1R expression and increases Angiotensin II levels, suggesting that the mechanisms by which 20-HETE promotes hypertension include activation of RAS that is likely initiated at the level of ACE induction. PMID:20837888

  18. The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy

    PubMed Central

    Pang, Hui; Han, Bing; Yu, Tao; Peng, Zhen

    2014-01-01

    Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n?=?32) were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day) or 5% glucose injection (GS). Sham-operated rats (n?=?8) received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson’s trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2) protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-?/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition, and limiting apoptosis of cardiomyocytes and oxidative damage. PMID:24647357

  19. The Beneficial Effect of Suramin on Monocrotaline-Induced Pulmonary Hypertension in Rats

    PubMed Central

    Izikki, Mohamed; Mercier, Olaf; Lecerf, Florence; Lubert Guin, Lauriane; Hoang, Eric; Dorfmüller, Peter; Perros, Frédéric; Humbert, Marc; Simonneau, Gerald; Dartevelle, Philippe; Fadel, Elie; Eddahibi, Saadia

    2013-01-01

    Background Pulmonary hypertension (PH) is a progressive disorder characterized by an increase in pulmonary artery pressure and structural changes in the pulmonary vasculature. Several observations indicate that growth factors play a key role in PH by modulating pulmonary artery smooth muscle cell (PA-SMC) function. In rats, established monocrotaline-induced PH (MCT-PH) can be reversed by blocking platelet-derived growth factor receptors (PDGF-R), epidermal growth factor receptors (EGF-R), or fibroblast growth factor receptors (FGF-R). All these receptors belong to the receptor tyrosine kinase (RTK) family. Methods and Results We evaluated whether RTK blockade by the nonspecific growth factor inhibitor, suramin, reversed advanced MCT-PH in rats via its effects on growth-factor signaling pathways. We found that suramin inhibited RTK and ERK1/2 phosphorylation in cultured human PA-SMCs. Suramin inhibited PA-SMC proliferation induced by serum, PDGF, FGF2, or EGF in vitro and ex vivo. Treatment with suramin from day 1 to day 21 after monocrotaline injection attenuated PH development, as shown by lower values for pulmonary artery pressure, right ventricular hypertrophy, and distal vessel muscularization on day 21 compared to control rats. Treatment with suramin from day 21 to day 42 after monocrotaline injection reversed established PH, thereby normalizing the pulmonary artery pressure values and vessel structure. Suramin treatment suppressed PA-SMC proliferation and attenuated both the inflammatory response and the deposition of collagen. Conclusions RTK blockade by suramin can prevent MCT-PH and reverse established MCT-PH in rats. This study suggests that an anti-RTK strategy that targets multiple RTKs could be useful in the treatment of pulmonary hypertension. PMID:24143201

  20. Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

    NASA Technical Reports Server (NTRS)

    Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

    1998-01-01

    We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

  1. Pulmonary Hypertension

    PubMed Central

    Newman, John H.

    2005-01-01

    The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation–perfusion relationships, lung–heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

  2. Effect of a second metal on cadmium-induced hypertension. [Rats

    SciTech Connect

    Perry, H.M. Jr.; Erlanger, M.W.; Perry, E.F.

    1983-03-01

    One percent salt, 1 ppm cadmium, or 1 ppm lead in drinking water caused similar mild hypertension in rats. The hypertensive effect of salt, given for 4 months beginning at weaning, disappeared when the salt was withdrawn but subsequently returned without further exposure. Rats continuously given 1 ppm cadmium during and after salt exposure were continuously hypertensive, but salt did not increase their hypertension. Rats continuously exposed to cadmium or cadmium plus lead without extra salt remained hypertensive for 20 months. Rats exposed to cadmium or cadmium plus lead for months 4 through 8 remained hypertensive after metal exposure was discontinued; addition of 0.35 ppm selenium corrected the hypertension in cadmium-fed rats but had little effect in the cadmium plus lead exposed rats.

  3. Prevalence and clinical correlates of the hypertensive disorders of pregnancy at Tikur Anbessa Hospital, Addis Ababa, Ethiopia.

    PubMed

    Teklu, Sisay; Gaym, Asheber

    2006-01-01

    A one-year longitudinal study was conducted at Tikur Anbessa central referral Hospital to assess the prevalence of hypertensive disorders of pregnancy (HDP), to see the socio-demographic and clinical parameters and pregnancy outcome of pregnancies afflicted by these complications. Out of 3424 deliveries conducted during the study period, 183 (5.3%) mothers were found to have one form of hypertensive disorders of pregnancy, 85.2% were cases of pregnancy induced hypertension (PIH),the majority (78.2%) were severe pre eclampsia and eclampsia; the remaining 14.8% had pregnancy aggravated hypertension (PAH) or chronic hypertension. Preterm delivery rate was 48.6% for all cases of HDP. Intervention rate was high with 44.3% induction of labor and 44.3% caesarian section, which is much higher than the over all intervention rate in the hospital's obstetric population during the studied period. Prenatal mortality rate (PNMR), case fatality rate (CFR) and intra uterine growth restriction (IUGR) were 300/1000 deliveries, 27/1000 deliveries and 41.6% respectively in mothers with HDP. Severe hypertension, high urine protein and high uric acid level were found to be associated with higher CFR, and poor prenatal outcome. The study provides base line data on HDP in a hospital obstetric population in Ethiopia. Important peculiar findings in this study were a very high rate of severe disease, PNMR and CFR compared to other institutional studies. There is a need to conduct nation wide multi center study on HDP in order to have national base line data on this important pregnancy complication. PMID:17447359

  4. Gestational Exposure to Elevated Testosterone Levels Induces Hypertension via Heightened Vascular Angiotensin II Type 1 Receptor Signaling in Rats1

    PubMed Central

    Chinnathambi, Vijayakumar; More, Amar S.; Hankins, Gary D.; Yallampalli, Chandra; Sathishkumar, Kunju

    2014-01-01

    ABSTRACT Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K+ depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. PMID:24855104

  5. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  6. ANG II-induced hypertension in the VCD mouse model of menopause is prevented by estrogen replacement during perimenopause.

    PubMed

    Pollow, Dennis P; Romero-Aleshire, Melissa J; Sanchez, Jessica N; Konhilas, John P; Brooks, Heddwen L

    2015-12-15

    Premenopausal females are resistant to the development of hypertension, and this protection is lost after the onset of menopause, resulting in a sharp increase in disease onset and severity. However, it is unknown how a fluctuating ovarian hormone environment during the transition from perimenopause to menopause impacts the onset of hypertension, and whether interventions during perimenopause prevent disease onset after menopause. A gradual transition to menopause was induced by repeated daily injections of 4-vinylcyclohexene diepoxide (VCD). ANG II (800 ng·kg(-1)·min(-1)) was infused into perimenopausal and menopausal female mice for 14 days. A separate cohort of mice received 17?-estradiol replacement during perimenopause. ANG II infusion produced significantly higher mean arterial pressure (MAP) in menopausal vs. cycling females, and 17?-estradiol replacement prevented this increase. In contrast, MAP was not significantly different when ANG II was infused into perimenopausal and cycling females, suggesting that female resistance to ANG II-induced hypertension is intact during perimenopause. ANG II infusion caused a significant glomerular hypertrophy, and hypertrophy was not impacted by hormonal status. Expression levels of aquaporin-2 (AQP2), a collecting duct protein, have been suggested to reflect blood pressure. AQP2 protein expression was significantly downregulated in the renal cortex of the ANG II-infused menopause group, where blood pressure was increased. AQP2 expression levels were restored to control levels with 17?-estradiol replacement. This study indicates that the changing hormonal environment in the VCD model of menopause impacts the severity of ANG II-induced hypertension. These data highlight the utility of the ovary-intact VCD model of menopause as a clinically relevant model to investigate the physiological mechanisms of hypertension that occur in women during the transition into menopause. PMID:26491098

  7. Activation of peroxisome proliferator-activated receptor ? ameliorates monocrotaline-induced pulmonary arterial hypertension in rats

    PubMed Central

    XIE, XINMING; WANG, GUIZUO; ZHANG, DEXIN; ZHANG, YONGHONG; ZHU, YANTING; LI, FANGWEI; LI, SHAOJUN; LI, MANXIANG

    2015-01-01

    Activation of peroxisome proliferator-activated receptor ? (PPAR?) suppresses the proliferation of pulmonary artery smooth muscle cells (PASMCs) and vascular remodeling in rats and humans, and therefore improves the development of pulmonary arterial hypertension (PAH). However, molecular mechanisms underlying these effects have not been completely understood. In the present study, the effects of PPAR? activation in monocrotaline (MCT)-induced pulmonary artery remodeling in rats were investigated. Eighteen Sprague-Dawley (SD) rats were randomly assigned into three groups (n=6): Control (Con), PAH and PAH treated with rosiglitazone (MCT + Rosi). The right ventricular systolic pressure (RVSP), the ratio of the right to left ventricle plus septum weight [RV/(LV + S)], the percentage of medial wall thickness (%MT) and wall area (%WA) were used to evaluate the development of PAH. Tissue morphology was measured using hematoxylin and eosin staining. The protein levels of the phosphatase and tensin homologue deleted on chromosome ten (PTEN), Akt (ser473) phosphorylation (p-Akt) and total Akt in intrapulmonary arteries were determined by western blot analysis. MCT treatment significantly increased the RVSP, which was reduced by rosiglitazone treatment. The ratio of RV/(LV + S), %MT and %WA induced by MCT were similarly inhibited, which was associated with the increase of PTEN expression and the inhibition of Akt phosphorylation levels by rosiglitazone. In conclusion, activation of PPAR? ameliorates the proliferation of PASMCs and vascular remodeling by regulating the PTEN/PI3K/Akt pathway, suggesting that the activation of PPAR? has potential benefits for PAH. PMID:26171162

  8. Protective Effect of Enalapril against Methionine-Enriched Diet-Induced Hypertension: Role of Endoplasmic Reticulum and Oxidative Stress

    PubMed Central

    Zhou, Yanfen; Zhao, Lianyou; Zhang, Zhimin; Lu, Xuanhao

    2015-01-01

    In the present study, we investigated the effect of methionine-enriched diet (MED) on blood pressure in rats and examined the protective effect of enalapril, a widely used angiotensin converting enzyme inhibitors (ACEi) class antihypertensive drug. The results showed that MED induced significant increase of SBP and Ang II-induced contractile response in aortae of rats. MED significantly increased plasma levels of homocysteine (Hcy) and ACE. In addition, MED increased the phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2 (eIF2?) and expression of activating transcription factor 3 (ATF3) and ATF6 in aortae of rats, indicating the occurrence of endoplasmic reticulum (ER) stress. Moreover, MED resulted in oxidative stress as evidenced by significant increase of TBARS level and decrease of superoxide dismutase and catalase activities. Administration of enalapril could effectively inhibit these pathological changes induced by MED in rats. These results demonstrated that ACE-mediated ER stress and oxidative stress played an important role in high Hcy-induced hypertension and MED may exert a positive loop between the activation of ACE and accumulation of Hcy, aggravating the pathological condition of hypertension. The data provide novel insights into the mechanism of high Hcy-associated hypertension and the therapeutic efficiency of enalapril. PMID:26640794

  9. Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs.

    PubMed

    Grasemann, Hartmut; Dhaliwal, Rupinder; Ivanovska, Julijana; Kantores, Crystal; McNamara, Patrick J; Scott, Jeremy A; Belik, Jaques; Jankov, Robert P

    2015-03-15

    Arginase is an enzyme that limits substrate L-arginine bioavailability for the production of nitric oxide by the nitric oxide synthases and produces L-ornithine, which is a precursor for collagen formation and tissue remodeling. We studied the pulmonary vascular effects of arginase inhibition in an established model of repeated systemic bleomycin sulfate administration in neonatal rats that results in pulmonary hypertension and lung injury mimicking the characteristics typical of bronchopulmonary dysplasia. We report that arginase expression is increased in the lungs of bleomycin-exposed neonatal rats and that treatment with the arginase inhibitor amino-2-borono-6-hexanoic acid prevented the bleomycin-induced development of pulmonary hypertension and deposition of collagen. Arginase inhibition resulted in increased L-arginine and L-arginine bioavailability and increased pulmonary nitric oxide production. Arginase inhibition also normalized the expression of inducible nitric oxide synthase, and reduced bleomycin-induced nitrative stress while having no effect on bleomycin-induced inflammation. Our data suggest that arginase is a promising target for therapeutic interventions in neonates aimed at preventing lung vascular remodeling and pulmonary hypertension. PMID:25595650

  10. Insulin resistance and its potential role in pregnancy-induced hypertension.

    PubMed

    Seely, Ellen W; Solomon, Caren G

    2003-06-01

    New-onset hypertension (which includes preeclampsia and gestational hypertension) is a common and morbid complication of pregnancy. Many features of the insulin resistance syndrome have been associated with this condition. These include hypertension, hyperinsulinemia, glucose intolerance, obesity, and lipid abnormalities. Other accompanying abnormalities may include elevated levels of leptin, TNFalpha, tissue plasminogen activator, plasminogen activator inhibitor-1, and testosterone. The documentation of these features before the onset of hypertension in pregnancy suggests that insulin resistance or associated abnormalities may have a role in this disorder. Furthermore, the recognition that features of the insulin resistance syndrome persist many years after pregnancy among women with this condition raises the possibility that these women may have increased risk for future cardiovascular disease. These observations suggest that interventions to reduce insulin resistance may reduce the risk of both hypertension in pregnancy and later life cardiovascular complications, and warrant further study. PMID:12788833

  11. Altered lymphatic function and architecture in salt-induced hypertension assessed by near-infrared fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Kwon, Sunkuk; Agollah, Germaine D.; Chan, Wenyaw; Sevick-Muraca, Eva M.

    2012-08-01

    The lymphatic system plays an important role in maintaining the fluid homeostasis between the blood vascular and interstitial tissue compartment and there is recent evidence that its transport capabilities may regulate blood pressure in salt-induced hypertension. Yet, there is little known how the lymphatic contractile function and architecture responds to dietary salt-intake. Thus, we longitudinally characterized lymphatic contractile function and vessel remodeling noninvasively using dynamic near-infrared fluorescence imaging in animal models of salt-induced hypertension. The lymphatics of mice and rats were imaged following intradermal injection of indocyanine green to the ear tip or the base of the tail before and during two weeks of either a high salt diet (HSD) or normal chow. Our noninvasive imaging data demonstrated dilated lymphatic vessels in the skin of mice and rats on a HSD as compared to their baseline levels. In addition, our dynamic imaging results showed increased lymphatic contraction frequency in HSD-fed mice and rats. Lymphatic contractile function and vessel remodeling occurs in response to salt-induced hypertension suggesting a possible role for the lymphatics in the regulation of vascular blood pressure.

  12. Effect of age on insulin-induced endothelin release and vasoreactivity in hypertriglyceridemic and hypertensive rats.

    PubMed

    Rubio, María Esther; Baños, Guadalupe; Díaz, Eulises; Guarner, Verónica

    2006-03-01

    In the present paper, the age-related changes in the vasoconstrictive endothelin-mediated response to insulin in aortas of normal and hypertensive, hypertriglyceridemic, hyperinsulinemic (HTG) rats were studied. To develop HTG rats, weanling male Wistar animals were given 30% sucrose in their drinking water for 4, 6, 12 and 18 months. Blood pressure was increased in HTG rats for up to 12 months showing a maximum at 6 months (138.9+/-0.8 mmHg). In vitro contractions were elicited with 40 mM KCl in the presence and absence 50 microU/ml insulin and of endothelin-receptor antagonists BQ123 and BQ788. Tension development to KCl was not modified during aging in control rats but was increased at 4 and 6 months in HTG rats. Increased endothelin release induced by insulin remained constant in normal rats, while in HTG rats it was higher than in controls at all ages. ET(A) blocker participation alone increased during aging in control rats while both receptor blockers participated in HTG rats. Our results suggest that the vasoconstrictive capacity to KCl plus insulin decreases during aging and that this decrease is greater in HTG rats. The participation of endothelin receptors in the aging process differs in control and HTG rats. PMID:16427233

  13. Cold-restraint induced gastric lesions in normotensive and spontaneously hypertensive rats

    SciTech Connect

    Athey, G.R.; Iams, S.G.

    1981-02-23

    Spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats were subjected to 2 hr of cold-restraint stress at 4-6/sup o/C following a 24 hr fast. WKY rats had a significantly greater incidence and degree of ulceration of the gastric glandular mucosa than did SHR rats. Mean arterial pressure, obtained from a chronic arterial cannula, fell during 2 hr of cold-restraint stress in both SHR and WKY rats. Heart rate was unchanged in WKY but fell significantly in SHR. Plasma norepinephrine (NE) and epinephrine (E), determined by radioenzymatic assay, increased significantly following stress. Increased levels of NE remained similar for both SHR and WKY rats, while post-stress levels of E for the SHR rats greatly exceeded E levels for WKY rats. A greater degree of hypothermia was also noted in SHR rats. Decreased stress induced ulcerogenesis in the SHR may be due to the well-known altered hemodynamic and autonomic nervous system reactivity in this strain or other factors not yet discovered.

  14. Ruscogenin exerts beneficial effects on monocrotaline-induced pulmonary hypertension by inhibiting NF-?B expression

    PubMed Central

    Zhu, Rong; Bi, Liqing; Kong, Hui; Xie, Weiping; Hong, Yongqing; Wang, Hong

    2015-01-01

    This study aims to examine the effect of ruscogenin on pulmonary arterial hypertension (PAH) and to determine the mechanism underlying this effect. We isolated pulmonary vascular smooth muscle cells (PVSMCs) from the pulmonary artery of the rats; the PVSMCs were cultured in vitro and then were treated with platelet-derived growth factor (PDGF), PDGF + ruscogenin, or PDGF + ruscogenin + parthenolide. We randomized Sprague-Dawley rats into five groups as follows: control group, PAH group, low-dose group, medium-dose group, and high-dose group; the rats in the low-, medium-, and high-dose groups received the vehicle and ruscogenin 0.1, 0.4, and 0.7 mg/kg, respectively, from day 1 to day 21 after injection of monocrotaline (MCT). We measured the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP), and medial wall thickness of the pulmonary artery (PAWT). We examined the levels of the nuclear factor kappa B (NF-?B) protein by using immunohistochemistry and western blot analysis, and the mRNA levels of NF-?B in PVSMCs were evaluated using real-time polymerase chain reaction (PCR). The mPAP, RVSP, and PAWT and the protein and mRNA levels of NF-?B were significantly higher in the PAH model group than in the control group (P < 0.05). Ruscogenin induced a significant dose-dependent decrease in the mPAP, RVSP, and PAWT and in the NF-?B expression in the PAH group (P < 0.05), which suggests that ruscogenin will also exert dose-dependent effects on MCT-induced PAH through the inhibition of NF-?B. PMID:26722401

  15. Pregnancy-Induced Hypertensive Disorders before and after a National Economic Collapse: A Population Based Cohort Study

    PubMed Central

    Eiríksdóttir, Védís Helga; Valdimarsdóttir, Unnur Anna; Ásgeirsdóttir, Tinna Laufey; Hauksdóttir, Arna; Lund, Sigrún Helga; Bjarnadóttir, Ragnheiður Ingibjörg; Cnattingius, Sven; Zoëga, Helga

    2015-01-01

    Background Data on the potential influence of macroeconomic recessions on maternal diseases during pregnancy are scarce. We aimed to assess potential change in prevalence of pregnancy-induced hypertensive disorders (preeclampsia and gestational hypertension) during the first years of the major national economic recession in Iceland, which started abruptly in October 2008. Methods and Findings Women whose pregnancies resulted in live singleton births in Iceland in 2005–2012 constituted the study population (N = 35,211). Data on pregnancy-induced hypertensive disorders were obtained from the Icelandic Medical Birth Register and use of antihypertensive drugs during pregnancy, including ?-blockers and calcium channel blockers, from the Icelandic Medicines Register. With the pre-collapse period as reference, we used logistic regression analysis to assess change in pregnancy-induced hypertensive disorders and use of antihypertensives during the first four years after the economic collapse, adjusting for demographic and pregnancy characteristics, taking aggregate economic indicators into account. Compared with the pre-collapse period, we observed an increased prevalence of gestational hypertension in the first year following the economic collapse (2.4% vs. 3.9%; adjusted odds ratio [aOR] 1.47; 95 percent confidence interval [95%CI] 1.13–1.91) but not in the subsequent years. The association disappeared completely when we adjusted for aggregate unemployment rate (aOR 1.04; 95% CI 0.74–1.47). Similarly, there was an increase in prescription fills of ?-blockers in the first year following the collapse (1.9% vs.3.1%; aOR 1.43; 95% CI 1.07–1.90), which disappeared after adjusting for aggregate unemployment rate (aOR 1.05; 95% CI 0.72–1.54). No changes were observed for preeclampsia or use of calcium channel blockers between the pre- and post-collapse periods. Conclusions Our data suggest a transient increased risk of gestational hypertension and use of ?-blockers among pregnant women in Iceland in the first and most severe year of the national economic recession. PMID:26379126

  16. Central Renin-Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II-Elicited Hypertension.

    PubMed

    Xue, Baojian; Thunhorst, Robert L; Yu, Yang; Guo, Fang; Beltz, Terry G; Felder, Robert B; Johnson, Alan Kim

    2016-01-01

    Obesity has been shown to promote renin-angiotensin system activity and inflammation in the brain and to be accompanied by increased sympathetic activity and blood pressure. Our previous studies demonstrated that administration of a subpressor dose of angiotensin (Ang) II sensitizes subsequent Ang II-elicited hypertension. The present study tested whether high-fat diet (HFD) feeding also sensitizes the Ang II-elicited hypertensive response and whether HFD-induced sensitization is mediated by an increase in renin-angiotensin system activity and inflammatory mechanisms in the brain. HFD did not increase baseline blood pressure, but enhanced the hypertensive response to Ang II compared with a normal-fat diet. The sensitization produced by the HFD was abolished by concomitant central infusions of either a tumor necrosis factor-? synthesis inhibitor, pentoxifylline, an Ang II type 1 receptor blocker, irbesartan, or an inhibitor of microglial activation, minocycline. Furthermore, central pretreatment with tumor necrosis factor-? mimicked the sensitizing action of a central subpressor dose of Ang II, whereas central pentoxifylline or minocycline abolished this Ang II-induced sensitization. Real-time quantitative reverse transcription-polymerase chain reaction analysis of lamina terminalis tissue indicated that HFD feeding, central tumor necrosis factor-?, or a central subpressor dose of Ang II upregulated mRNA expression of several components of the renin-angiotensin system and proinflammatory cytokines, whereas inhibition of Ang II type 1 receptor and of inflammation reversed these changes. The results suggest that HFD-induced sensitization of Ang II-elicited hypertension is mediated by upregulation of the brain renin-angiotensin system and of central proinflammatory cytokines. PMID:26573717

  17. Targeting mitochondrial reactive oxygen species to modulate hypoxia-induced pulmonary hypertension.

    PubMed

    Adesina, Sherry E; Kang, Bum-Yong; Bijli, Kaiser M; Ma, Jing; Cheng, Juan; Murphy, Tamara C; Michael Hart, C; Sutliff, Roy L

    2015-10-01

    Pulmonary hypertension (PH) is characterized by increased pulmonary vascular remodeling, resistance, and pressures. Reactive oxygen species (ROS) contribute to PH-associated vascular dysfunction. NADPH oxidases (Nox) and mitochondria are major sources of superoxide (O2(•-)) and hydrogen peroxide (H2O2) in pulmonary vascular cells. Hypoxia, a common stimulus of PH, increases Nox expression and mitochondrial ROS (mtROS) production. The interactions between these two sources of ROS generation continue to be defined. We hypothesized that mitochondria-derived O2(•-) (mtO2(•-)) and H2O2 (mtH2O2) increase Nox expression to promote PH pathogenesis and that mitochondria-targeted antioxidants can reduce mtROS, Nox expression, and hypoxia-induced PH. Exposure of human pulmonary artery endothelial cells to hypoxia for 72h increased mtO2(•-) and mtH2O2. To assess the contribution of mtO2(•-) and mtH2O2 to hypoxia-induced PH, mice that overexpress superoxide dismutase 2 (Tg(hSOD2)) or mitochondria-targeted catalase (MCAT) were exposed to normoxia (21% O2) or hypoxia (10% O2) for three weeks. Compared with hypoxic control mice, MCAT mice developed smaller hypoxia-induced increases in RVSP, ?-SMA staining, extracellular H2O2 (Amplex Red), Nox2 and Nox4 (qRT-PCR and Western blot), or cyclinD1 and PCNA (Western blot). In contrast, Tg(hSOD2) mice experienced exacerbated responses to hypoxia. These studies demonstrate that hypoxia increases mtO2(•-) and mtH2O2. Targeting mtH2O2 attenuates PH pathogenesis, whereas targeting mtO2(•-) exacerbates PH. These differences in PH pathogenesis were mirrored by RVSP, vessel muscularization, levels of Nox2 and Nox4, proliferation, and H2O2 release. These studies suggest that targeted reductions in mtH2O2 generation may be particularly effective in preventing hypoxia-induced PH. PMID:26073127

  18. Optical cryoimaging of rat kidney and the effective role of chromosome 13 in salt-induced hypertension

    NASA Astrophysics Data System (ADS)

    Salehpour, F.; Yang, C.; Kurth, T.; Cowley, A. W.; Ranji, M.

    2015-03-01

    The objective of this work is to assess oxidative stress levels in salt-sensitive hypertension animal model using 3D optical cryoimager to image mitochondrial redox ratio. We studied Dahl salt-induced (SS) rats, and compared the results with a consomic SS rat strain (SSBN13). The SSBN13 strain was developed by the introgression of chromosome from the Brown Norway (BN) rat into the salt-sensitive (SS) genetic background and exhibits significant protection from salt induced hypertension1 . These two groups were fed on a high salt diet of 8.0% NaCl for one week. Mitochondrial redox ratio (NADH/FAD=NADH RR), was used as a quantitative marker of the oxidative stress in kidney tissue. Maximum intensity projected images and their corresponding histograms in each group were acquired from each kidney group. The result showed a 49% decrease in mitochondrial redox ratio of SS compared to SSBN13 translated to an increase in the level of oxidative stress of the tissue. Therefore, the results quantify oxidative stress levels and its effect on mitochondrial redox in salt sensitive hypertension.

  19. Pregnancy termination in patients with pregnancy-induced hypertension or eclampsia at less than 22 weeks' gestation.

    PubMed

    Sampson, M B; Thomason, J L; Tomasi, A M; Work, B A

    1982-06-15

    3 patients with fetal death, 2 of whom had pregnancy-induced hypertension and a third with eclampsia had pregnancy termination before 22 weeks' gestation with vaginal prostaglandin E2 (PGE2) suppositories, without complication. PGE2 has a hypotensive action, decreasing blood pressure by arteriolar dilation and blocking the angiotensin-induced rise in blood pressure in the pregnant rhesus monkey and should be useful abortifacient in patients with hypertension including preeclampsia and eclampsia. One patient received magnesium sulfate and the other 2 received hydralazine and methyldopa during PGE2 administration which could alter mean arterial pressure (MAP). MAPs remained stable and dropped slightly after PGE2 administration in the 2nd and 3rd patients. These outcomes suggest that PGE2 suppositories can be used to terminate 2nd trimester pregnancy in cases of hypertension and eclampsia when routine medical management is ineffective or when fetal death occurs although caution is advised since severe hypotension can occur with PGE2 administration. PMID:6953765

  20. Alpha-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats.

    PubMed

    Wang, Mofei; Tanida, Mamoru; Shibamoto, Toshishige; Kurata, Yasutaka

    2013-10-15

    Anaphylactic shock is sometimes life-threatening, and it is accompanied by hepatic venoconstriction in animals, which, in part, accounts for anaphylactic hypotension. Roles of norepinephrine and ?-adrenoceptor in anaphylaxis-induced hypotension and portal hypertension were investigated in anesthetized ovalbumin-sensitized Sprague-Dawley rats. The sensitized rats were randomly allocated to the following pretreatment groups (n = 6/group): 1) control (nonpretreatment), 2) ?1-adrenoceptor antagonist prazosin, 3) nonselective ?-adrenoceptor antagonist phentolamine, 4) 6-hydroxydopamine-induced chemical sympathectomy, and 5) surgical hepatic sympathectomy. Anaphylactic shock was induced by an intravenous injection of the antigen. The systemic arterial pressure (SAP), central venous pressure (CVP), portal venous pressure (PVP), and portal venous blood flow (PBF) were measured, and splanchnic [Rspl: (SAP-PVP)/PBF] and portal venous [Rpv: (PVP-CVP)/PBF] resistances were determined. Separately, we measured efferent hepatic sympathetic nerve activity during anaphylaxis. In the control group, SAP markedly decreased, followed by a gradual recovery toward baseline. PVP and Rpv increased 3.2- and 23.3-fold, respectively, after antigen. Rspl decreased immediately, but only transiently, after antigen, and then increased 1.5-fold later than 10 min. The ?-adrenoceptor antagonist pretreatment or chemical sympathectomy inhibited the late increase in Rspl and the SAP recovery. Pretreatment with ?-adrenoceptor antagonists, or either chemical or surgical hepatic sympathectomy, did not affect the antigen-induced increase in Rpv. Hepatic sympathetic nerve activity did not significantly change after antigen. In conclusion, ?-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats. Hepatic sympathetic nerves are not involved in anaphylactic portal hypertension. PMID:23948775

  1. Insight into molecular mechanisms of ultrafine carbon particle induced cardiovascular impairments in spontaneously hypertensive rats.

    EPA Science Inventory

    Rationale: Exposure to ambient particulate matter is a risk factor for cardiopulmonary disease as identified in several epidemiological studies. Radio telemetric analysis detected increased heart rate and blood pressure in Spontaneously Hypertensive Rats (SHR) following inhalatio...

  2. Supplementation of DETA/NO attenuates cold stress induced pulmonary hypertension syndrome in broilers 

    E-print Network

    Thompson, Michel Ann

    2002-01-01

    The anatomical and physiological structure of avians increases the broiler chicken's susceptibility to pulmonary hypertension syndrome (PHS). This has been a continual problem in the poultry industry costing millions of dollars annually. Studies...

  3. Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates neurohormonal excitation in high salt-induced hypertension.

    PubMed

    Zhang, Meng; Qin, Da-Nian; Suo, Yu-Ping; Su, Qing; Li, Hong-Bao; Miao, Yu-Wang; Guo, Jing; Feng, Zhi-Peng; Qi, Jie; Gao, Hong-Li; Mu, Jian-Jun; Zhu, Guo-Qing; Kang, Yu-Ming

    2015-06-15

    Reactive oxygen species (ROS) in the brain plays an important role in the progression of hypertension and hydrogen peroxide (H2O2) is a major component of ROS. The aim of this study is to explore whether endogenous H2O2 changed by polyethylene glycol-catalase (PEG-CAT) and aminotriazole (ATZ) in the hypothalamic paraventricular nucleus (PVN) regulates neurotransmitters, renin-angiotensin system (RAS), and cytokines, and whether subsequently affects the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in high salt-induced hypertension. Male Sprague-Dawley rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 10 weeks. Then rats were treated with bilateral PVN microinjection of PEG-CAT (0.2 i.u./50nl), an analog of endogenous catalase, the catalase inhibitor ATZ (10nmol/50nl) or vehicle. High salt-fed rats had significantly increased MAP, RSNA, plasma norepinephrine (NE) and pro-inflammatory cytokines (PICs). In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 (subunits of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), interleukin-1beta (IL-1?), glutamate and NE, and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN than normal diet rats. Bilateral PVN microinjection of PEG-CAT attenuated the levels of RAS and restored the balance of neurotransmitters and cytokines, while microinjection of ATZ into the PVN augmented those changes occurring in hypertensive rats. Our findings demonstrate that ROS component H2O2 in the PVN regulating MAP and RSNA are partly due to modulate neurotransmitters, renin-angiotensin system, and cytokines within the PVN in salt-induced hypertension. PMID:25891026

  4. Vascular Smooth Muscle Sirtuin-1 Protects Against Aortic Dissection During Angiotensin II–Induced Hypertension

    PubMed Central

    Fry, Jessica L; Shiraishi, Yasunaga; Turcotte, Raphaël; Yu, Xunjie; Gao, Yuan Z; Akiki, Rachid; Bachschmid, Markus; Zhang, Yanhang; Morgan, Kathleen G; Cohen, Richard A; Seta, Francesca

    2015-01-01

    Background Sirtuin-1 (SirT1), a nicotinamide adenine dinucleotide+–dependent deacetylase, is a key enzyme in the cellular response to metabolic, inflammatory, and oxidative stresses; however, the role of endogenous SirT1 in the vasculature has not been fully elucidated. Our goal was to evaluate the role of vascular smooth muscle SirT1 in the physiological response of the aortic wall to angiotensin II, a potent hypertrophic, oxidant, and inflammatory stimulus. Methods and Results Mice lacking SirT1 in vascular smooth muscle (ie, smooth muscle SirT1 knockout) had drastically high mortality (70%) caused by aortic dissection after angiotensin II infusion (1 mg/kg per day) but not after an equipotent dose of norepinephrine, despite comparable blood pressure increases. Smooth muscle SirT1 knockout mice did not show any abnormal aortic morphology or blood pressure compared with wild-type littermates. Nonetheless, in response to angiotensin II, aortas from smooth muscle SirT1 knockout mice had severely disorganized elastic lamellae with frequent elastin breaks, increased oxidant production, and aortic stiffness compared with angiotensin II–treated wild-type mice. Matrix metalloproteinase expression and activity were increased in the aortas of angiotensin II–treated smooth muscle SirT1 knockout mice and were prevented in mice overexpressing SirT1 in vascular smooth muscle or with use of the oxidant scavenger tempol. Conclusions Endogenous SirT1 in aortic smooth muscle is required to maintain the structural integrity of the aortic wall in response to oxidant and inflammatory stimuli, at least in part, by suppressing oxidant-induced matrix metalloproteinase activity. SirT1 activators could potentially be a novel therapeutic approach to prevent aortic dissection and rupture in patients at risk, such as those with hypertension or genetic disorders, such as Marfan’s syndrome. PMID:26376991

  5. Identification of a Novel Mucin Gene HCG22 Associated With Steroid-Induced Ocular Hypertension

    PubMed Central

    Jeong, Shinwu; Patel, Nitin; Edlund, Christopher K.; Hartiala, Jaana; Hazelett, Dennis J.; Itakura, Tatsuo; Wu, Pei-Chang; Avery, Robert L.; Davis, Janet L.; Flynn, Harry W.; Lalwani, Geeta; Puliafito, Carmen A.; Wafapoor, Hussein; Hijikata, Minako; Keicho, Naoto; Gao, Xiaoyi; Argüeso, Pablo; Allayee, Hooman; Coetzee, Gerhard A.; Pletcher, Mathew T.; Conti, David V.; Schwartz, Stephen G.; Eaton, Alexander M.; Fini, M. Elizabeth

    2015-01-01

    Purpose. The pathophysiology of ocular hypertension (OH) leading to primary open-angle glaucoma shares many features with a secondary form of OH caused by treatment with glucocorticoids, but also exhibits distinct differences. In this study, a pharmacogenomics approach was taken to discover candidate genes for this disorder. Methods. A genome-wide association study was performed, followed by an independent candidate gene study, using a cohort enrolled from patients treated with off-label intravitreal triamcinolone, and handling change in IOP as a quantitative trait. Results. An intergenic quantitative trait locus (QTL) was identified at chromosome 6p21.33 near the 5? end of HCG22 that attained the accepted statistical threshold for genome-level significance. The HCG22 transcript, encoding a novel mucin protein, was expressed in trabecular meshwork cells, and expression was stimulated by IL-1, and inhibited by triamcinolone acetate and TGF-?. Bioinformatic analysis defined the QTL as an approximately 4 kilobase (kb) linkage disequilibrium block containing 10 common single nucleotide polymorphisms (SNPs). Four of these SNPs were identified in the National Center for Biotechnology Information (NCBI) GTEx eQTL browser as modifiers of HCG22 expression. Most are predicted to disrupt or improve motifs for transcription factor binding, the most relevant being disruption of the glucocorticoid receptor binding motif. A second QTL was identified within the predicted signal peptide of the HCG22 encoded protein that could affect its secretion. Translation, O-glycosylation, and secretion of the predicted HCG22 protein was verified in cultured trabecular meshwork cells. Conclusions. Identification of two independent QTLs that could affect expression of the HCG22 mucin gene product via two different mechanisms (transcription or secretion) is highly suggestive of a role in steroid-induced OH. PMID:25813999

  6. Evaluation of Exercise-Induced Hypertension Post Endovascular Stenting of Coarctation of Aorta

    PubMed Central

    Mortazaeian, Hojat; Moghadam, Mohammad Yoosef Aarabi; Ghaderian, Mehdi; Davary, Paridokht Nakhostin; Meraji, Mohmood; Mohammadi, Akbar Shah

    2010-01-01

    Background: Coarctation of the aorta (COA) is a defect that accounts for 5–8% of all congenital heart diseases. Balloon angioplasty as a treatment for COA is increasingly performed, with endovascular stents having been proposed as a means of improving the efficacy and safety of the procedure. The aim of this study was to evaluate the systolic blood pressure gradient at rest and during maximal exercise at follow-up in patients post endovascular stenting of COA. Methods: Thirteen patients (4 native and 9 re-coarctation cases of COA after surgery or balloon angioplasty) with a mean age of 11.1 ± 4.7 years underwent endovascular stenting between November 2007 and December 2009 via standard techniques for native COA as an alternative to surgical repair. Doppler echocardiography was performed pre and post stenting. Resting and exercise assessment of blood pressure was performed at follow-up. Results: Post stent implantation, no angiographic major complications were evident. Systolic blood pressure gradient decreased from 42 ± 8.8 mm Hg before stent placement to 7 ± 10 mm Hg at follow-up (p value < 0.001). Peak Doppler pressure gradient decreased from 30 ± 14 mm Hg to 14 ± 10 mm Hg at follow-up (p value < 0.007). One case of exercise-induced hypertension was seen in patients. Conclusion: Endovascular stenting for native COA in older children and post-surgical COA repair in patients with residual COA and re-coarctation is a reasonable alternative to surgical correction. During early follow-up, stenting effectively alleviates the aortic arch obstruction with normalization of the systemic blood pressure both at rest and during maximal exercise. PMID:23074582

  7. Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats

    PubMed Central

    Kagota, Satomi; Tamashiro, Akiko; Yamaguchi, Yu; Sugiura, Reiko; Kuno, Takayoshi; Nakamura, Kazuki; Kunitomo, Masaru

    2001-01-01

    Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an important role in vasodilatation and blood pressure regulation. We investigated the effects of high salt intake on the nitric oxide (NO)?–?cyclic GMP signal transduction pathway regulating relaxation in aortas of spontaneously hypertensive rats (SHR).Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a normal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks.In aortic rings from SHR, endothelium-dependent relaxations in response to acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A23187 were significantly impaired by the high salt intake. The endothelium-independent relaxations in response to sodium nitroprusside (SNP) and nitroglycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchanged. On the other hand, high salt diet had no significant effects on the relaxations of aortic rings from WKY.In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SNP was decreased by the high salt intake.Western blot analysis showed that the protein level of endothelial NO synthase (eNOS) was slightly increased, whereas that of soluble guanylate cyclase (sGC) was dramatically reduced by the high salt intake.These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which leads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not the eNOS/NO pathway. PMID:11606313

  8. The role of sustained release isosorbide mononitrate on corticosteroid-induced hypertension in healthy human subjects.

    PubMed

    Williamson, P M; Ong, S L H; Whitworth, J A; Kelly, J J

    2015-12-01

    There is evidence implicating abnormalities in the nitric oxide (NO) pathway in the development of glucocorticoid-induced hypertension (GC-HT). In humans, a reduction in NO availability during cortisol treatment has been observed. This study examined whether the NO donation may reverse the elevated blood pressure (BP) observed with cortisol treatment. A randomised double-blind, placebo-controlled, crossover study was undertaken in eight healthy men to address the effect of co-administration of isosorbide mononitrate (ISMN, 60?mg single dose, day 5) with cortisol (200?mg per day, days 1-6) and then compared with placebo (single dose, day 5) with cortisol. After a 2-week washout period, subjects crossed over to the alternate treatment. BP measurements were obtained using a mercury sphygmomanometer. Tonometry was used to estimate central pressures. There was a significant rise in mean arterial pressure with cortisol: 80±3 vs 89±3?mm?Hg (day 1 vs day 5, cortisol+ISMN phase, P<0.001) and 81±3 vs 89±3?mm?Hg (day 1 vs day 5, cortisol+placebo phase, P<0.01). ISMN significantly decreased aortic augmentation index: -17.3±3.2 vs 1.8±3.5%, (differences calculated from day 5-day 1, cortisol/ISMN vs cortisol+placebo, P<0.001). These results demonstrated that GC-HT can be modified by co-administration of exogenous NO donors, consistent with the hypothesis that GC-HT is accompanied by reduced NO activity in humans. PMID:25810066

  9. Onset and Regression of Pregnancy-Induced Cardiac Alterations in Gestationally Hypertensive Mice: The Role of the Natriuretic Peptide System.

    PubMed

    Ventura, Nicole M; Li, Terry Y; Tse, M Yat; Andrew, R David; Tayade, Chandrakant; Jin, Albert Y; Pang, Stephen C

    2015-12-01

    Pregnancy induces cardiovascular adaptations in response to increased volume overload. Aside from the hemodynamic changes that occur during pregnancy, the maternal heart also undergoes structural changes. However, cardiac modulation in pregnancies complicated by gestational hypertension is incompletely understood. The objectives of the current investigation were to determine the role of the natriuretic peptide (NP) system in pregnancy and to assess alterations in pregnancy-induced cardiac hypertrophy between gestationally hypertensive and normotensive dams. Previously we have shown that mice lacking the expression of atrial NP (ANP; ANP(-/-)) exhibit a gestational hypertensive phenotype. In the current study, female ANP(+/+) and ANP(-/-) mice were mated with ANP(+/+) males. Changes in cardiac size and weight were evaluated across pregnancy at Gestational Days 15.5 and 17.5 and Postnatal Days 7, 14, and 28. Nonpregnant mice were used as controls. Physical measurement recordings and histological analyses demonstrated peak cardiac hypertrophy occurring at 14 days postpartum in both ANP(+/+) and ANP(-/-) dams with little to no change during pregnancy. Additionally, left ventricular expression of the renin-angiotensin system (RAS) and NP system was quantified by real-time quantitative polymerase chain reaction. Up-regulation of Agt and AT1a genes was observed late in pregnancy, while Nppa and Nppb genes were significantly up-regulated postpartum. Our data suggest that pregnancy-induced cardiac hypertrophy may be influenced by the RAS throughout gestation and by the NP system postpartum. Further investigations are required to gain a complete understanding of the mechanistic aspects of pregnancy-induced cardiac hypertrophy. PMID:26536903

  10. Nebivolol induces distinct changes in profibrosis microRNA expression compared with atenolol, in salt-sensitive hypertensive rats.

    PubMed

    Ye, Hongmei; Ling, Shukuan; Castillo, Alexander C; Thomas, Bejoy; Long, Bo; Qian, Jinqiao; Perez-Polo, Jose R; Ye, Yumei; Chen, Xiaoping; Birnbaum, Yochai

    2013-05-01

    Nebivolol is a selective ?1-blocker with nitric oxide-enhancing effects. MicroRNAs are small noncoding RNA molecules that downregulate gene expression. We compared the effects of nebivolol and atenolol, a first generation ?1-selective blocker, on left ventricular hypertrophy, fibrosis, and function and microRNA expression in a rodent model of hypertension. Dahl salt-sensitive rats received either low-salt chow (control) or AIN-76A high-salt (8% NaCl) diet and randomized to vehicle (high-salt), nebivolol (20 mg/kg per day), or atenolol (50 mg/kg per day) for 8 weeks. High-salt induced left ventricular hypertrophy and fibrosis and decreased the expression of miR-27a, -29a, and -133a. Nebovolol attenuated deterioration of left ventricular systolic function, remodeling, and fibrosis more than atenolol, despite similar effects on heart rate and blood pressure. Nebivolol, but not atenolol, prevented the decrease in miR-27a and -29a induced by high-salt. Nebivolol and atenolol equally attenuated the decrease in miR-133a. In vitro overexpression of miR-27a,-29a, and -133a inhibited cardiomyocyte hypertrophy and reduced collagen expression. Both miR-27a and -29a target Sp1, and miR-133a targets Cdc42. Pharmacological inhibition of Sp1 and Cdc42 decreased myocardial fibrosis and hypertrophy. Our data support a differential microRNAs expression profile in salt-induced hypertension. Nebivolol substantially attenuated cardiac remodeling, hypertrophy, and fibrosis more than atenolol. These effects are related to attenuation of the hypertension-induced decrease in miR-27a and -29a (with a subsequent decrease in Sp1 expression) and miR-133a (with a subsequent decrease in Cdc42). PMID:23460283

  11. Prolonged Subcutaneous Administration of Oxytocin Accelerates Angiotensin II-Induced Hypertension and Renal Damage in Male Rats

    PubMed Central

    Phie, James; Haleagrahara, Nagaraja; Newton, Patricia; Constantinoiu, Constantin; Sarnyai, Zoltan; Chilton, Lisa; Kinobe, Robert

    2015-01-01

    Oxytocin and its receptor are synthesised in the heart and blood vessels but effects of chronic activation of this peripheral oxytocinergic system on cardiovascular function are not known. In acute studies, systemic administration of low dose oxytocin exerted a protective, preconditioning effect in experimental models of myocardial ischemia and infarction. In this study, we investigated the effects of chronic administration of low dose oxytocin following angiotensin II-induced hypertension, cardiac hypertrophy and renal damage. Angiotensin II (40 ?g/Kg/h) only, oxytocin only (20 or 100 ng/Kg/h), or angiotensin II combined with oxytocin (20 or 100 ng/Kg/h) were infused subcutaneously in adult male Sprague-Dawley rats for 28 days. At day 7, oxytocin or angiotensin-II only did not change hemodynamic parameters, but animals that received a combination of oxytocin and angiotensin-II had significantly elevated systolic, diastolic and mean arterial pressure compared to controls (P < 0.01). Hemodynamic changes were accompanied by significant left ventricular cardiac hypertrophy and renal damage at day 28 in animals treated with angiotensin II (P < 0.05) or both oxytocin and angiotensin II, compared to controls (P < 0.01). Prolonged oxytocin administration did not affect plasma concentrations of renin and atrial natriuretic peptide, but was associated with the activation of calcium-dependent protein phosphatase calcineurin, a canonical signalling mechanism in pressure overload-induced cardiovascular disease. These data demonstrate that oxytocin accelerated angiotensin-II induced hypertension and end-organ renal damage, suggesting caution should be exercised in the chronic use of oxytocin in individuals with hypertension. PMID:26393919

  12. Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk

    PubMed Central

    Gamella-Pozuelo, Luis; Fuentes-Calvo, Isabel; Gómez-Marcos, Manuel A.; Recio-Rodriguez, José I.; Agudo-Conde, Cristina; Fernández-Martín, José L.; Cannata-Andía, Jorge B.; López-Novoa, José M.; García-Ortiz, Luis; Martínez-Salgado, Carlos

    2015-01-01

    Abstract The search for biomarkers of hypertension and diabetes-induced damage to multiple target organs is a priority. We analyzed the correlation between plasma cardiotrophin-1 (CT-1), a chemokine that participates in cardiovascular remodeling and organ fibrosis, and a wide range of parameters currently used to diagnose morphological and functional progressive injury in left ventricle, arteries, and kidneys of diabetic and hypertensive patients, in order to validate plasma levels of CT-1 as clinical biomarker. This is an observational study with 93 type 2-diabetic patients, 209 hypertensive patients, and 82 healthy controls in which we assessed the following parameters: plasma CT-1, basal glycaemia, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), left ventricular hypertrophy (LVH by electrocardiographic indexes), peripheral vascular disease (by pulse wave velocity—PWV, carotid intima-media thickness—C-IMT, and ankle-brachial index—ABI), and renal impairment (by microalbuminuria, albumin/creatinine urinary ratio, plasma creatinine concentrations, and glomerular filtration rate). Hypertensive or diabetic patients have higher plasma CT-1 than control patients. CT-1 positively correlates with basal glycaemia, SBP, DBP, PP, LVH, arterial damage (increased IMT, decreased ABI), and early renal damage (microalbuminuria, elevated albumin/creatinine ratio). CT-1 also correlates with increased 10-year cardiovascular risk. Multiple linear regression analysis confirmed that CT-1 was associated with arterial injury assessed by PWV, IMT, ABI, and cardiac damage evaluated by Cornell voltage duration product. Increases in plasma CT-1 are strongly related to the intensity of several parameters associated to target organ damage supporting further investigation of its diagnostic capacity as single biomarker of cardiovascular injury and risk and, possibly, of subclinical renal damage. PMID:26222851

  13. Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk.

    PubMed

    Gamella-Pozuelo, Luis; Fuentes-Calvo, Isabel; Gómez-Marcos, Manuel A; Recio-Rodriguez, José I; Agudo-Conde, Cristina; Fernández-Martín, José L; Cannata-Andía, Jorge B; López-Novoa, José M; García-Ortiz, Luis; Martínez-Salgado, Carlos

    2015-07-01

    The search for biomarkers of hypertension and diabetes-induced damage to multiple target organs is a priority. We analyzed the correlation between plasma cardiotrophin-1 (CT-1), a chemokine that participates in cardiovascular remodeling and organ fibrosis, and a wide range of parameters currently used to diagnose morphological and functional progressive injury in left ventricle, arteries, and kidneys of diabetic and hypertensive patients, in order to validate plasma levels of CT-1 as clinical biomarker.This is an observational study with 93 type 2-diabetic patients, 209 hypertensive patients, and 82 healthy controls in which we assessed the following parameters: plasma CT-1, basal glycaemia, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), left ventricular hypertrophy (LVH by electrocardiographic indexes), peripheral vascular disease (by pulse wave velocity-PWV, carotid intima-media thickness-C-IMT, and ankle-brachial index-ABI), and renal impairment (by microalbuminuria, albumin/creatinine urinary ratio, plasma creatinine concentrations, and glomerular filtration rate).Hypertensive or diabetic patients have higher plasma CT-1 than control patients. CT-1 positively correlates with basal glycaemia, SBP, DBP, PP, LVH, arterial damage (increased IMT, decreased ABI), and early renal damage (microalbuminuria, elevated albumin/creatinine ratio). CT-1 also correlates with increased 10-year cardiovascular risk. Multiple linear regression analysis confirmed that CT-1 was associated with arterial injury assessed by PWV, IMT, ABI, and cardiac damage evaluated by Cornell voltage duration product.Increases in plasma CT-1 are strongly related to the intensity of several parameters associated to target organ damage supporting further investigation of its diagnostic capacity as single biomarker of cardiovascular injury and risk and, possibly, of subclinical renal damage. PMID:26222851

  14. Combined inhibition of 20-hydroxyeicosatetraenoic acid formation and of epoxyeicosatrienoic acids degradation attenuates hypertension and hypertension-induced end-organ damage in Ren-2 transgenic rats

    PubMed Central

    ?ertíková Chábová, V?ra; Walkowska, Agnieszka; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kujal, Petr; Vernerová, Zdena; Va?ourková, Zdenka; Kopkan, Libor; Kramer, Herbert J.; Falck, John R.; Imig, John D.; Hammock, Bruce D.; Van??ková, Ivana; ?ervenka, Lud?k

    2010-01-01

    Recent studies have shown that the renal cytochrome P-450 metabolites of arachidonic acid: the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE), and the vasodilator epoxyeicosatrienoic acids (EETs) play an important role in the pathophysiology of angiotensin II (ANG II)-dependent forms of hypertension and the associated target organ damage. The present studies were performed in Ren-2 renin transgenic rats (TGR) to evaluate the effects of chronic selective inhibition of 20-HETE formation or elevation of the level of EETs, alone or in combination, on the course of hypertension and hypertension-associated end-organ damage. Both young (30 days of age) prehypertensive TGR and adult (190 days of age) TGR with established hypertension were examined. Normotensive Hannover Sprague-Dawley (HanSD) rats served as controls. The rats were treated with N-methylsulfonyl-12,12-dibromododec-11-enamide to inhibit 20-HETE formation and/or with N-cyclohexyl-N-dodecyl urea to inhibit soluble epoxide hydrolase and prevent degradation of EETs. Inhibition in TGR rats of 20-HETE formation combined with enhanced bioavailability of EETs attenuated the development of hypertension, cardiac hypertrophy, proteinuria, glomerular hypertrophy and sclerosis as well as renal tubulointerstitial injury. This was also associated with an attenuation of the responsiveness of the systemic and renal vascular beds to ANG II without modifying their responses to norepinephrine. Our data suggest that altered production and/or action of 20-HETE and EETs plays a permissive role in the development of hypertension and hypertension-associated end-organ damage in this model of ANG II-dependent hypertension. This information provides a basis for a search of new therapeutic approaches to the treatment of hypertension. PMID:20050826

  15. [Endocrine hypertension in pregnancy].

    PubMed

    Launay-Mignot, P; Roueff, S; Tropeano, A-I; Thaunat, O; Plouin, P F

    2002-10-01

    Hypertension is a frequent complication of pregnancy and may compromise fetal and maternal outcome. Hypertension may be pregnancy-induced, essential or secondary to endocrine disorders. Most cases of endocrine hypertension are the consequence of adrenal diseases. Pheochromocytoma, hypercorticism, primary aldosteronism or glucocorticoid-remediable aldosteronism can be present or diagnosed at any term and may cause severe hypertension. The most hazardous form of endocrine hypertension during pregnancy is pheochromocytoma because it may involve paroxysmal arrhythmia and/or hypertension during labor. Clinical clues and biological tests are similar to those used in non-pregnant subjects. Tests for tumor location are limited to ultrasound and magnetic resonance scans in order to avoid maternal and fetal irradiation. Medication to prepare for pheochromocytoma surgery uses alpha- and beta-blockers. The timing of surgery depends on the term of pregnancy at the diagnosis of the tumor. PMID:12442092

  16. Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats.

    PubMed

    Ahmed, Lamiaa A; Obaid, Al Arqam Z; Zaki, Hala F; Agha, Azza M

    2014-10-01

    Pulmonary hypertension is a progressive disease of various origins that is associated with right ventricular dysfunction. In the present study, the protective effect of diosgenin was investigated in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). Diosgenin (100 mg/kg) was given by oral administration once daily for 3 weeks. At the end of the experiment, mean arterial blood pressure, electrocardiography and echocardiography were recorded. Rats were then sacrificed and serum was separated for determination of total nitrate/nitrite level. Right ventricles and lungs were isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha, total nitrate/nitrite and transforming growth factor-beta contents. Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible nitric oxide synthase protein expression were also determined. Moreover, histological analysis of pulmonary arteries and cardiomyocyte cross-sectional area was performed. Diosgenin treatment provided a significant improvement toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline in rats. Furthermore, diosgenin therapy prevented monocrotaline-induced changes in nitric oxide production, endothelial and inducible nitric oxide synthase protein expression as well as histological analysis. These findings support the beneficial effect of diosgenin in pulmonary hypertension induced by monocrotaline in rats. PMID:25062790

  17. Prenatal programming of pulmonary hypertension induced by chronic hypoxia or ductal ligation in sheep

    PubMed Central

    2013-01-01

    Abstract Pulmonary hypertension of the newborn is caused by a spectrum of functional and structural abnormalities of the cardiopulmonary circuit. The existence of multiple etiologies and an incomplete understanding of the mechanisms of disease progression have hindered the development of effective therapies. Animal models offer a means of gaining a better understanding of the fundamental basis of the disease. To that effect, a number of experimental animal models are being used to generate pulmonary hypertension in the fetus and newborn. In this review, we compare the mechanisms associated with pulmonary hypertension caused by two such models: in utero ligation of the ductus arteriosus and chronic perinatal hypoxia in sheep fetuses and newborns. In this manner, we make direct comparisons between ductal ligation and chronic hypoxia with respect to the associated mechanisms of disease, since multiple studies have been performed with both models in a single species. We present evidence that the mechanisms associated with pulmonary hypertension are dependent on the type of stress to which the fetus is subjected. Such an analysis allows for a more thorough evaluation of the disease etiology, which can help focus clinical treatments. The final part of the review provides a clinical appraisal of current treatment strategies and lays the foundation for developing individualized therapies that depend on the causative factors. PMID:25006393

  18. Diesel Exhaust-Induced Pulmonary and Cardiovascular Impairment: The Role of Hypertension Intervention

    EPA Science Inventory

    Background–Exposure to diesel exhaust (DE) particles and associated gases is linked to cardiovascular impairments; however the susceptibility of hypertensive individuals is less well understood. Objective–1) To determine cardiopulmonary effects of gas-phase versus whole-DE, and 2...

  19. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain.

    PubMed

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-Il

    2011-11-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  20. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain

    PubMed Central

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

    2011-01-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  1. Renoprotective mechanisms of pirfenidone in hypertension-induced renal injury: through anti-fibrotic and anti-oxidative stress pathways.

    PubMed

    Ji, Xu; Naito, Yukiko; Weng, Huachun; Ma, Xiao; Endo, Kosuke; Kito, Naoko; Yanagawa, Nariaki; Yu, Yang; Li, Jie; Iwai, Naoharu

    2013-01-01

    Pirfenidone (PFD) is a novel anti-fibrotic agent that targets TGF?. However, the mechanisms underlying its renoprotective properties in hypertension-induced renal injury are poorly understood. We investigated the renoprotective properties of PFD and clarified its renoprotective mechanisms in a rat hypertension-induced renal injury model. Dahl salt-sensitive rats were fed a high-salt diet with or without 1% PFD for 6 weeks. During the administration period, we examined the effects of PFD on blood pressure and renal function. After the administration, the protein levels of renal TGF?, Smad2/3, TNF?, MMP9, TIMP1, and catalase were examined. In addition, total serum antioxidant activity was measured. Compared to untreated rats, PFD treatment significantly attenuated blood pressure and proteinuria. Histological study showed that PFD treatment improved renal fibrosis. PFD may exert its anti-fibrotic effects via the downregulation of TGF?-Smad2/3 signaling, improvement of MMP9/TIMP1 balance, and suppression of fibroblast proliferation. PFD treatment also increased catalase expression and total serum antioxidant activity. In contrast, PFD treatment did not affect the expression of TNF? protein, macrophage or T-cell infiltration, or plasma interleukin 1? levels. PFD prevents renal injury via its anti-fibrotic and anti-oxidative stress mechanisms. Clarifying the renoprotective mechanisms of PFD will help improve treatment for chronic renal diseases. PMID:24389407

  2. Vascular smooth muscle Jak2 mediates angiotensin II-induced hypertension via increased levels of reactive oxygen species

    PubMed Central

    Kirabo, Annet; Kearns, Patrick N.; Jarajapu, Yagna P.; Sasser, Jennifer M.; Oh, Suk Paul; Grant, Maria B.; Kasahara, Hideko; Cardounel, Arturo J.; Baylis, Chris; Wagner, Kay-Uwe; Sayeski, Peter P.

    2011-01-01

    Aims Angiotensin II (Ang II) type AT1 receptors expressed on vascular smooth muscle cells (VSMCs) couple to the Jak2 signalling pathway. However, the importance of this tissue-specific coupling is poorly understood. The purpose of this investigation was to determine the importance of VSMC-derived Jak2 in angiotensin II-mediated hypertension. Methods and results The Cre-loxP system was used to conditionally eliminate Jak2 tyrosine kinase expression within the smooth muscle cells of mice. Following chronic Ang II infusion, the resulting increase in mean arterial pressure (MAP) was significantly attenuated in the Jak2 null mice when compared with littermate controls. The VSMC Jak2 null mice were also protected from the Ang II-induced vascular remodelling. Aortic rings from the VSMC Jak2 null mice exhibited reduced Ang II-induced contraction and enhanced endothelial-dependent relaxation via increased nitric oxide (NO) bioavailability. When compared with controls, the VSMC Jak2 nulls also had lower levels of hydrogen peroxide, Rho kinase activity, and intracellular Ca2+ in response to Ang II. Conclusions The data indicate that VSMC Jak2 expression is involved in the pathogenesis of Ang II-dependent hypertension due to the increased presence of reactive oxygen species (ROS). As such, VSMC-derived Jak2 tyrosine kinase modulates overall vascular tone via multiple, non-redundant mechanisms. PMID:21354995

  3. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension

    PubMed Central

    Fowler, Ewan D.; Benoist, David; Drinkhill, Mark J.; Stones, Rachel; Helmes, Michiel; Wüst, Rob C.I.; Stienen, Ger J.M.; Steele, Derek S.; White, Ed

    2015-01-01

    Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control animals. In vivo right ventricular diastolic pressure–volume relationships were measured in anesthetized animals; diastolic force–length relationships in single enzymatically dissociated myocytes and myocardial creatine kinase levels by Western blot. We observed diastolic dysfunction in right ventricular failure indicated by significantly steeper diastolic pressure–volume relationships in vivo and diastolic force–length relationships in single myocytes. There was a significant reduction in creatine kinase protein expression in failing right ventricle. Dysfunction also manifested as a shorter diastolic sarcomere length in failing myocytes. This was associated with a Ca2 +-independent mechanism that was sensitive to cross-bridge cycling inhibition. In saponin-skinned failing myocytes, addition of exogenous creatine kinase significantly lengthened sarcomeres, while in intact healthy myocytes, inhibition of creatine kinase significantly shortened sarcomeres. Creatine kinase inhibition also changed the relatively flat contraction amplitude–stimulation frequency relationship of healthy myocytes into a steeply negative, failing phenotype. Decreased creatine kinase expression leads to diastolic dysfunction. We propose that this is via local reduction in ATP:ADP ratio and thus to Ca2 +-independent force production and diastolic sarcomere shortening. Creatine kinase inhibition also mimics a definitive characteristic of heart failure, the inability to respond to increased demand. Novel therapies for pulmonary artery hypertension are needed. Our data suggest that cardiac energetics would be a potential ventricular therapeutic target. PMID:26116865

  4. Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

    PubMed

    Pereira, Thiago A; Syn, Wing-Kin; Machado, Mariana V; Vidigal, Paula V; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M; Santos, Elisângela T; Chan, Isaac S; Trindade, Guilherme V M; Choi, Steve S; Witek, Rafal P; Pereira, Fausto E; Secor, William E; Andrade, Zilton A; Lambertucci, José Roberto; Diehl, Anna Mae

    2015-11-01

    Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity. PMID:26201095

  5. Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni

    PubMed Central

    Pereira, Thiago A.; Syn, Wing-Kin; Machado, Mariana V.; Vidigal, Paula V.; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M.; Santos, Elisângela T.; Chan, Isaac S.; Trindade, Guilherme V.M.; Choi, Steve S.; Witek, Rafal P.; Pereira, Fausto E.; Secor, William E.; Andrade, Zilton A.; Lambertucci, José Roberto

    2015-01-01

    Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity. PMID:26201095

  6. Effect of ACE inhibitor on DOCA-salt- and aortic coarctation-induced hypertension in mice: do kinin B2 receptors play a role?

    PubMed

    Rhaleb, N E; Peng, H; Alfie, M E; Shesely, E G; Carretero, O A

    1999-01-01

    Kinins have been shown to play an important role in the cardioprotective effect of ACE inhibitors (ACEi) during heart failure and ischemia-reperfusion. However, it is controversial as to whether kinins oppose the hypertensinogenic effect of deoxycorticosterone acetate plus salt (DOCA-salt) or aortic coarctation and whether they mediate both chronic antihypertensive and cardiac antihypertrophic effects of ACEi in hypertension. Using normal 129/SvEvTac mice and mice lacking the bradykinin B2 receptor gene (B2-KO), we investigated whether (1) the hypertensinogenic effect of DOCA-salt or aortic coarctation is enhanced in B2-KO mice and (2) the chronic antihypertensive and antihypertrophic effects of an ACEi (ramipril, 4 mg. kg-1. d-1) are mediated by B2 receptors in aortic coarctation (6 weeks)- and DOCA-salt (4 weeks)-induced hypertension. Before surgery, there was no difference between 129/SvEvTac and B2-KO mice in terms of blood pressure and heart weight, suggesting that kinins are not essential to maintaining normal blood pressure. DOCA-salt (volume expansion) or aortic coarctation (renin-dependent) induced similar hypertension and left ventricular hypertrophy (LVH) in 129/SvEvTac and B2-KO mice, suggesting that kinins do not play an essential role in the development of DOCA-salt- or aortic coarctation-induced hypertension. We found that B2 receptors mediate only the early (1 week) but not the late phase (4 weeks) of the chronic hypotensive effect of ACEi in DOCA-salt hypertension. On the other hand, chronic ACE inhibition prevented the development of hypertension and LVH in both 129/SvEvTac and B2-KO mice given DOCA-salt or subjected to aortic coarctation, suggesting that kinins do not participate in the chronic antihypertensive and antihypertrophic effects of ACEi in these 2 models of hypertension. Thus, in mice, kinins acting via B2 receptors do not participate in (1) maintenance of normal basal blood pressure, (2) establishment and maintenance of hypertension induced by DOCA-salt or aortic coarctation, and (3) chronic antihypertensive and cardiac antihypertrophic effects of ACEi in DOCA-salt and aortic coarctation hypertension. PMID:9931125

  7. Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity

    PubMed Central

    Kelley, Eric E.; Baust, Jeff; Bonacci, Gustavo; Golin-Bisello, Franca; Devlin, Jason E.; St. Croix, Claudette M.; Watkins, Simon C.; Gor, Sonia; Cantu-Medellin, Nadiezhda; Weidert, Eric R.; Frisbee, Jefferson C.; Gladwin, Mark T.; Champion, Hunter C.; Freeman, Bruce A.; Khoo, Nicholas K.H.

    2014-01-01

    Aims Obesity is a risk factor for diabetes and cardiovascular diseases, with the incidence of these disorders becoming epidemic. Pathogenic responses to obesity have been ascribed to adipose tissue (AT) dysfunction that promotes bioactive mediator secretion from visceral AT and the initiation of pro-inflammatory events that induce oxidative stress and tissue dysfunction. Current understanding supports that suppressing pro-inflammatory and oxidative events promotes improved metabolic and cardiovascular function. In this regard, electrophilic nitro-fatty acids display pleiotropic anti-inflammatory signalling actions. Methods and results It was hypothesized that high-fat diet (HFD)-induced inflammatory and metabolic responses, manifested by loss of glucose tolerance and vascular dysfunction, would be attenuated by systemic administration of nitrooctadecenoic acid (OA-NO2). Male C57BL/6j mice subjected to a HFD for 20 weeks displayed increased adiposity, fasting glucose, and insulin levels, which led to glucose intolerance and pulmonary hypertension, characterized by increased right ventricular (RV) end-systolic pressure (RVESP) and pulmonary vascular resistance (PVR). This was associated with increased lung xanthine oxidoreductase (XO) activity, macrophage infiltration, and enhanced expression of pro-inflammatory cytokines. Left ventricular (LV) end-diastolic pressure remained unaltered, indicating that the HFD produces pulmonary vascular remodelling, rather than LV dysfunction and pulmonary venous hypertension. Administration of OA-NO2 for the final 6.5 weeks of HFD improved glucose tolerance and significantly attenuated HFD-induced RVESP, PVR, RV hypertrophy, lung XO activity, oxidative stress, and pro-inflammatory pulmonary cytokine levels. Conclusions These observations support that the pleiotropic signalling actions of electrophilic fatty acids represent a therapeutic strategy for limiting the complex pathogenic responses instigated by obesity. PMID:24385344

  8. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice

    PubMed Central

    Lee, Craig R.; Imig, John D.; Edin, Matthew L.; Foley, Julie; DeGraff, Laura M.; Bradbury, J. Alyce; Graves, Joan P.; Lih, Fred B.; Clark, James; Myers, Page; Perrow, A. Ligon; Lepp, Adrienne N.; Kannon, M. Alison; Ronnekleiv, Oline K.; Alkayed, Nabil J.; Falck, John R.; Tomer, Kenneth B.; Zeldin, Darryl C.

    2010-01-01

    Renal cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) regulate sodium transport and blood pressure. Although endothelial CYP-derived EETs are potent vasodilators, their contribution to the regulation of blood pressure remains unclear. Consequently, we developed transgenic mice with endothelial expression of the human CYP2J2 and CYP2C8 epoxygenases to increase endothelial EET biosynthesis. Compared to wild-type littermate controls, an attenuated afferent arteriole constrictor response to endothelin-1 and enhanced dilator response to acetylcholine was observed in CYP2J2 and CYP2C8 transgenic mice. CYP2J2 and CYP2C8 transgenic mice demonstrated modestly, but not significantly, lower mean arterial pressure under basal conditions compared to wild-type controls. However, mean arterial pressure was significantly lower in both CYP2J2 and CYP2C8 transgenic mice during coadministration of N-nitro-l-arginine methyl ester and indomethacin. In a separate experiment, a high-salt diet and subcutaneous angiotensin II was administered over 4 wk. The angiotensin/high-salt-induced increase in systolic blood pressure, proteinuria, and glomerular injury was significantly attenuated in CYP2J2 and CYP2C8 transgenic mice compared to wild-type controls. Collectively, these data demonstrate that increased endothelial CYP epoxygenase expression attenuates afferent arteriolar constrictor reactivity and hypertension-induced increases in blood pressure and renal injury in mice. We conclude that endothelial CYP epoxygenase function contributes to the regulation of blood pressure.—Lee, C. R., Imig, J. D., Edin, M. E., Foley, J., DeGraff, L. M., Bradbury, J. A., Graves, J. P., Lih, F. B., Clark, J., Myers, P., Perrow, A. L., Lepp, A. N., Kannon, M. A., Ronnekleiv, O. K., Alkayed, N. J., Falck, J. R., Tomer, K. B., Zeldin, D. C. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. PMID:20495177

  9. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension

    PubMed Central

    2011-01-01

    Background Involvement of inflammation in pulmonary hypertension (PH) has previously been demonstrated and recently, immune-modulating dendritic cells (DCs) infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH) and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS), as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. Methods We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT), monocrotaline-exposure/pneumonectomy (MCT/PE). Results Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine) in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature. Immunolabeling for OX62, CD68 and actin revealed adventitial and medial DC- and monocyte-infiltration; in MCT/PE, medial smooth muscle cells were admixed with CD68+/vimentin+ cells. Conclusion Our experimental findings support a new concept of immunologic responses to increased OS in MCT/PE-induced PAH, possibly linking recruitment of dendritic cells and OS-producing mast-cells to characteristic vasculopathy. PMID:21906276

  10. Cytochrome P4501A1 is Required for Vascular Dysfunction and Hypertension Induced by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    National Health and Nutrition Examination Survey data show an association between hypertension and exposure to dioxin-like halogenated aromatic hydrocarbons (HAH). Further, chronic exposure of mice to the prototypical HAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induces reactive oxygen species (...

  11. Exercise-Induced Pulmonary Artery Hypertension in a Patient with Compensated Cardiac Disease: Hemodynamic and Functional Response to Sildenafil Therapy

    PubMed Central

    Nikolaidis, Lazaros; Memon, Nabeel

    2015-01-01

    We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization—combined with the use of a symptom-limited, bedside bicycle ergometer—revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class. PMID:25873799

  12. Androgen-dependent hypertension is mediated by 20-HETE-induced vascular dysfunction: Role of IkappaB kinase

    PubMed Central

    Wu, Cheng-Chia; Cheng, Jennifer; Zhang, Frank Fan; Gotlinger, Katherine H.; Kelkar, Mukul; Zhang, Yilun; Jat, Jawahar L.; Falck, John R.; Schwartzman, Michal L.

    2011-01-01

    Increased vascular synthesis of 20-HETE is associated with increased vascular contraction, endothelial dysfunction and endothelial activation; all are believed to account for 20-HETE pro-hypertensive properties. We previously demonstrated that the 20-HETE-dependent inhibition of NO production is mediated through I?B kinase (IKK) suggesting a cross talk between 20-HETE-mediated endothelial dysfunction and activation. In this study, we examined the temporal relationship among blood pressure, endothelial dysfunction and endothelial activation and the role of IKK in the rat model of androgen-driven 20-HETE-mediated hypertension. In Sprague-Dawley rats treated with 5?-dihydrotestosterone (DHT), renal vascular 20-HETE levels increased by day 2 of treatment from 17.7±2.4 to 57.7±9.7 ng/mg, while blood pressure elevation reached significance by day 3 (132.7±1.7 vs 117.2±0.8 mmHg). In renal interlobar arteries, when compared to vehicle, DHT treatment increased the sensitivity to phenylephrine-induced vasoconstriction by 3.5-fold, decreased acetylcholine-induced vasorelaxation and increased NF-kB activity, all of which were attenuated by treatment with the 20-HETE antagonist, 20-HEDE. Co-treatment with parthenolide, an IKK inhibitor, attenuated the androgen-dependent 20-HETE-mediated elevation in blood pressure (from 133.7±3.1 to 109.8±3.0 mmHg). In addition, parthenolide treatment negated 20-HETE-mediated inhibition of the relaxing response to acetylcholine and 20-HETE-mediated increase in vascular NF-kB activity. These findings suggest that inhibition of IKK attenuates the androgen-dependent 20-HETE-mediated increase in blood pressure by inhibiting both 20-HETE-dependent endothelial activation and dysfunction. PMID:21321301

  13. Stress-Induced Sodium Excretion, a New Intermediate Phenotype to Study the Early Genetic Etiology of Hypertension?

    PubMed Central

    Ge, Dongliang; Su, Shaoyong; Zhu, Haidong; Dong, Yanbin; Wang, Xiaoling; Harshfield, Gregory A; Treiber, Frank A; Snieder, Harold

    2009-01-01

    Impaired stress-induced pressure natriuresis, i.e., an inadequate increase in urinary sodium excretion (UNaV) in response to a stress-induced blood pressure increase, may lead to the premature development of essential hypertension. To assess the heritability of baseline UNaV, stress UNaV, and the UNaV response to stress (?UNaV = stress UNaV – baseline UNaV), we studied 396 African American (AA) and 494 European American (EA) twins, including monozygotic and dizygotic of same- as well as opposite-sex (mean age: 17.6 ± 3.3; range: 11.9–30.0). Bivariate genetic model fitting was performed to examine the extent to which genetic and environmental factors are common or specific to baseline and stress UNaV. Heritability estimates for ?UNaV can be derived from these bivariate models. All bivariate analyses were performed separately in EAs and AAs, because univariate models for baseline UNaV showed significant ethnic differences in heritability estimates. Best fitting models showed that the heritability of stress UNaV was 0.42 in EAs and 0.58 in AAs. Only 15% and 11% of the total variance could be attributed to genetic factors common to baseline and stress UNaV in EAs and AAs, respectively. After removal of all shared influences with baseline UNaV, heritabilities for stress UNaV were 0.32 in EAs and 0.57 in AAs. Heritability estimates for ?UNaV were 0.36 in EAs and 0.39 in AAs. In summary, this study establishes ?UNaV and stress UNaV as heritable phenotypes that may be used to study the genetic etiology of early hypertension development. PMID:19104006

  14. Calcium/Calmodulin-Dependent Kinase II Inhibition in Smooth Muscle Reduces Angiotensin II–Induced Hypertension by Controlling Aortic Remodeling and Baroreceptor Function

    PubMed Central

    Prasad, Anand M; Morgan, Donald A; Nuno, Daniel W; Ketsawatsomkron, Pimonrat; Bair, Thomas B; Venema, Ashlee N; Dibbern, Megan E; Kutschke, William J; Weiss, Robert M; Lamping, Kathryn G; Chapleau, Mark W; Sigmund, Curt D; Rahmouni, Kamal; Grumbach, Isabella M

    2015-01-01

    Background Multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by angiotensin II (Ang II) in cultured vascular smooth muscle cells (VSMCs), but its function in experimental hypertension has not been explored. The aim of this study was to determine the impact of CaMKII inhibition selectively in VSMCs on Ang II hypertension. Methods and Results Transgenic expression of a CaMKII peptide inhibitor in VSMCs (TG SM-CaMKIIN model) reduced the blood pressure response to chronic Ang II infusion. The aortic depressor nerve activity was reset in hypertensive versus normotensive wild-type animals but not in TG SM-CaMKIIN mice, suggesting that changes in baroreceptor activity account for the blood pressure difference between genotypes. Accordingly, aortic pulse wave velocity, a measure of arterial wall stiffness and a determinant of baroreceptor activity, increased in hypertensive versus normotensive wild-type animals but did not change in TG SM-CaMKIIN mice. Moreover, examination of blood pressure and heart rate under ganglionic blockade revealed that VSMC CaMKII inhibition abolished the augmented efferent sympathetic outflow and renal and splanchnic nerve activity in Ang II hypertension. Consequently, we hypothesized that VSMC CaMKII controls baroreceptor activity by modifying arterial wall remodeling in Ang II hypertension. Gene expression analysis in aortas from normotensive and Ang II–infused mice revealed that TG SM-CaMKIIN aortas were protected from Ang II–induced upregulation of genes that control extracellular matrix production, including collagen. VSMC CaMKII inhibition also strongly altered the expression of muscle contractile genes under Ang II. Conclusions CaMKII in VSMCs regulates blood pressure under Ang II hypertension by controlling structural gene expression, wall stiffness, and baroreceptor activity. PMID:26077587

  15. Role of miR206 in genistein-induced rescue of pulmonary hypertension in monocrotaline model.

    PubMed

    Sharma, Salil; Umar, Soban; Centala, Alexander; Eghbali, Mansoureh

    2015-12-15

    Pulmonary hypertension (PH) is a progressive lung disease associated with proliferation of smooth muscle cells and constriction of lung microvasculature, leading to increased pulmonary arterial pressure, right ventricular failure, and death. We have previously shown that genistein rescues preexisting established PH by significantly improving lung and heart function. (Matori H, Umar S, Nadadur RD, Sharma S, Partow-Navid R, Afkhami M, Amjedi M, Eghbali M. Hypertension 60: 425-430, 2012). Here, we have examined the role of microRNAs (miRs) in the rescue action of genistein in monocrotaline (MCT)-induced PH in rats. Our miR microarray analysis on the lung samples from control, PH, and genistein-rescue group revealed that miR206, which was robustly upregulated to ?11-fold by PH, was completely normalized to control levels by genistein treatment. Next, we examined whether knockdown of miR206 could reverse preexisting established PH. PH was induced in male rats by 60 mg/kg of MCT, and rats received three intratracheal doses of either miR206 antagomir (10 mg/kg body wt) or scrambled miR control at days 17, 21, and 26. Knockdown of miR206 resulted in significant improvement in the cardiopulmonary function, as right ventricular pressure was significantly reduced to 38.6 ± 3.61 mmHg from 61.2 ± 5.4 mmHg in PH, and right ventricular hypertrophy index was decreased to 0.35 ± 0.04 from 0.59 ± 0.037 in PH. Knockdown of miR206 reversed PH-induced pulmonary vascular remodeling in vivo and was associated with restoration of PH-induced loss of capillaries in the lungs and induction of vascular endothelial growth factor A expression. In conclusion, miR206 antagomir therapy improves cardiopulmonary function and structure and rescues preexisting severe PH in MCT rat model possibly by stimulating angiogenesis in the lung. PMID:26472874

  16. The effect of hydroalcoholic extract of Ferula foetida stems on blood pressure and oxidative stress in dexamethasone-induced hypertensive rats

    PubMed Central

    Safaeian, Leila; Ghannadi, Alireza; Javanmard, Shaghayegh Haghjoo; Vahidian, Mohammad Hadi

    2015-01-01

    Ferula foetida (Bunge) Regel. is one of the most widespread and important Ferula species with nutritional and medicinal applications. Some phytochemicals with helpful cardiovascular effects have been isolated from Ferula species. The present study was designed to evaluate the effects of hydroalcoholic extract of the stems of F. foetida in dexamethasone (Dex)-induced hypertension in rats. Hypertension was induced by subcutaneous injection of Dex (30 µg/kg) for 14 days. In a prevention study, rats received oral F. foetida extract (200, 400 and 800 mg/kg) for 4 days prior to Dex administration and during the test period (Days 1-18). In a treatment study, F. foetida extract was administered from day 8 to 14. Systolic blood pressure (SBP) was evaluated using tail-cuff method. The thymus weight was measured as an indicator of glucocorticoid activity. The hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) were measured in plasma samples. Dex-induced hypertensive rats showed significant increases in SBP and in plasma H2O2 and decreases in the body and thymus weights and in FRAP value (P<0.001). Administration of F. foetida extract significantly prevented and reversed hypertension at all doses. It also increased plasma FRAP value (P<0.001) but failed to decrease plasma H2O2 concentration. These results suggest antihypertensive and antioxidant effects of F. foetida stem extract in Dex-induced hypertension. More investigations are needed to elucidate the exact mechanism of antihypertensive effect of this traditional phytomedicine. PMID:26600859

  17. Disulfiram-induced reversible hypertension: a prospective case series and review of the literature.

    PubMed

    Kulkarni, Ranganath R; Ramdurg, Santosh I; Bairy, Bhavya K

    2014-10-01

    Disulfiram (DSF) is one of the recommended aids in the management of selected patients with alcohol dependence. Hypertension (HTN) as an adverse effect of DSF therapy is less understood. In our prospective case series of 7 subjects with co-morbid alcohol and nicotine dependence, a temporal, dose-dependent, and reversible grade 1-3 HTN within 1-6 weeks of initiation of DSF therapy (125-500 mg/day) with no other detectable causes of HTN was noted. Challenges and strategies surrounding diagnosis and treatment along with mean change and percentage rise in blood pressure are described. Literature review and clinical description of case series may suggest neurobiological role in its causation. HTN may be a clinically significant, dose-dependent, and reversible adverse effect of DSF therapy, especially in co-morbid alcohol and nicotine-dependent patients. Awareness amongst clinicians may render better health care delivery to subjects with alcohol dependence. PMID:25336781

  18. N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

    PubMed Central

    2014-01-01

    Background The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function. Methods Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis. Results The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71?±?0.05 for MCT group to 0.50?±?0.06 for MCT?+?NAC group, p?

  19. Hypertension - overview

    MedlinePLUS Videos and Cool Tools

    If left untreated, hypertension can lead to the thickening of arterial walls causing its lumen, or blood passage way, to narrow in diameter. ... the narrowed arterial openings. In addition, people with hypertension may be more susceptible to stroke.

  20. Hypertensive Vasculopathy

    PubMed Central

    Park, Jeong Bae

    2014-01-01

    An exclusive interview by Prof. Jeong Bae Park conducted with Dr. Rhian M. Touyz in Seoul while she was visiting for the Korean Society of Hypertension, May 10, 2014. In this interview, Dr. Touyz explains and describes hypertensive vasculopathy.

  1. Hypertensive Crisis

    MedlinePLUS

    ... services (EMS), have someone drive you to the hospital right away. Hypertensive Urgency Hypertensive urgency is a situation where the blood ... symptoms: Severe headache Shortness of breath Nosebleeds Severe ... of hypertensive urgency generally requires readjustment and/or additional dosing of ...

  2. Role of angiotensin II in plasma PAI-1 changes induced by imidapril or candesartan in hypertensive patients with metabolic syndrome.

    PubMed

    Fogari, Roberto; Zoppi, Annalisa; Mugellini, Amedeo; Maffioli, Pamela; Lazzari, Pierangelo; Derosa, Giuseppe

    2011-12-01

    To evaluate the relationship between plasma plasminogen activator inhibitor-1 (PAI-1) and angiotensin II (Ang II) changes during treatment with imidapril and candesartan in hypertensive patients with metabolic syndrome. A total of 84 hypertensive patients with metabolic syndrome were randomized to imidapril 10?mg or candesartan 16?mg for 16 weeks. At weeks 4 and 8, there was a dose titration to imidapril 20?mg and candesartan 32?mg in nonresponders (systolic blood pressure (SBP) >140 and/or diastolic blood pressure (DBP) >90?mm?Hg). We evaluated, at baseline and after 2, 4, 8, 12 and 16 weeks, clinic blood pressure, Ang II and PAI-1 antigen. Both imidapril and candesartan induced a similar SBP/DBP reduction (-19.4/16.8 and -19.5/16.3?mm?Hg, respectively, P<0.001 vs. baseline). Both drugs decreased PAI-1 antigen after 4 weeks of treatment, but only the PAI-1 lowering effect of imidapril was sustained throughout the 16 weeks (-9.3?ng?ml(-1), P<0.01 vs. baseline), whereas candesartan increased PAI-1 (+6.5?ng?ml(-1), P<0.05 vs. baseline and P<0.01 vs. imidapril). Imidapril significantly decreased Ang II levels (-14.6?pg?ml(-1) at week 16, P<0.05 vs. baseline), whereas candesartan increased them (+24.2?pg?ml(-1), P<0.01 vs. baseline and vs. imidapril). In both groups there was a positive correlation between Ang II and PAI-1 changes (r=0.61, P<0.001 at week 16 for imidapril, and r=0.37, P<0.005 at week 16 for candesartan). Imidapril reduced plasma PAI-1 and Ang II levels, whereas candesartan increased them. This suggests that the different effect of angiotensin-converting enzyme inhibitors and Ang II blockers on Ang II production has a role in their different influence on fibrinolysis. PMID:21814211

  3. Serum levels of tumor necrosis factor-related apoptosis-inducing ligand correlate with the severity of pulmonary hypertension.

    PubMed

    Liu, Huan; Yang, Erli; Lu, Xiaolan; Zuo, Caojian; He, Yuhu; Jia, Daile; Zhu, Qian; Yu, Ying; Lv, Ankang

    2015-08-01

    Pulmonary hypertension (PH) is a rapidly progressive disease that eventually leads to right heart failure and death. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-Rs) play an important role in the survival, migration, and proliferation of vascular smooth muscle cells. However, the association between serum TRAIL levels and PH is unknown. In this study, we assayed the serum soluble TRAIL (sTRAIL) levels in 78 patients with PH and 80 controls. The sTRAIL concentrations were elevated in the PH patients compared with the controls (138.76 ± 6.60 pg/mL vs. 80.14 ± 3.38 pg/mL, p < 0.0001). The presence of sTRAIL levels of >103 pg/mL could discriminate PH patients from healthy individuals, with a sensitivity of 75.6% and specificity of 81.2%. Moreover, elevated sTRAIL concentrations were associated with eventual pathological complications; this is consistent with the finding that sTRAIL levels decreased in patients who responded to treatment. In a hypoxia-induced PH mouse model, sTRAIL levels were significantly higher compared with those in normoxia mice, and clearly decreased when the mice were treated with treprostinil. The sTRAIL levels were positively correlated with right ventricular systolic pressure and the index of right ventricular hypertrophy. In conclusion, serum sTRAIL could be a biomarker for diagnosis and effective therapy for PH patients. PMID:26086178

  4. Disruption of the Apelin-APJ System Worsens Hypoxia-Induced Pulmonary Hypertension

    PubMed Central

    Chandra, Suparna M.; Razavi, Hedi; Kim, Jongmin; Agrawal, Rani; Kundu, Ramendra; de Jesus Perez, Vinicio; Zamanian, Roham T.; Quertermous, Thomas; Chun, Hyung J.

    2011-01-01

    Objective The G-protein–coupled receptor APJ and its ligand apelin are highly expressed in the pulmonary vasculature, but their function in this vascular bed is unclear. We hypothesized that disruption of apelin signaling would lead to worsening of the vascular remodeling associated with pulmonary hypertension (PH). Methods and Results We found that apelin-null mice developed more severe PH compared with wild-type mice when exposed to chronic hypoxia. Microcomputed tomography of the pulmonary arteries demonstrated significant pruning of the microvasculature in the apelin-null mice. Apelin-null mice had a significant reduction of serum nitrate levels. This was secondary to downregulation of endothelial nitric oxide synthase (eNOS), which was associated with reduced expression of Kruppel-like factor 2, a known regulator of eNOS expression. In vitro knockdown studies targeting apelin in human pulmonary artery endothelial cells demonstrated decreased eNOS and Kruppel-like factor 2 expression, as well as impaired phosphorylation of AMP-activated kinase and eNOS. Moreover, serum apelin levels of patients with PH were significantly lower than those of controls. Conclusion These data demonstrate that disruption of apelin signaling can exacerbate PH mediated by decreased activation of AMP-activated kinase and eNOS, and they identify this pathway as a potentially important therapeutic target for treatment of this refractory human disease. PMID:21233449

  5. Early Macrophage Recruitment and Alternative Activation Are Critical for the Later Development of Hypoxia-induced Pulmonary Hypertension

    PubMed Central

    Vergadi, Eleni; Chang, Mun Seog; Lee, Changjin; Liang, Olin; Liu, Xianlan; Fernandez-Gonzalez, Angeles; Mitsialis, S. Alex; Kourembanas, Stella

    2011-01-01

    Background Lung inflammation precedes the development of hypoxia-induced pulmonary hypertension (HPH); however its role in the pathogenesis of HPH is poorly understood. We sought to characterize the hypoxic inflammatory response and elucidate its role in the development of HPH. We also aimed to investigate the mechanisms by which heme oxygenase-1 (HO-1), an anti-inflammatory enzyme, is protective in HPH. Methods and Results We generated bitransgenic mice that overexpress human HO-1 under doxycycline (dox) control in an inducible, lung-specific manner. Hypoxic exposure of mice in the absence of dox resulted in early transient accumulation of monocytes/macrophages in the bronchoalveolar lavage. Alveolar macrophages acquired an alternatively activated phenotype (M2) in response to hypoxia, characterized by the expression of Found in Inflammatory Zone-1, Arginase-1 and Chitinase-3-like-3. A brief, two-day pulse of dox delayed but did not prevent the peak of hypoxic inflammation, and could not protect from HPH. In contrast, a seven-day dox treatment sustained high HO-1 levels during the entire period of hypoxic inflammation, inhibited macrophage accumulation and activation, induced macrophage IL-10 expression, and prevented the development of HPH. Supernatants from hypoxic M2 macrophages promoted proliferation of pulmonary artery smooth muscle cells while treatment with carbon monoxide, a HO-1 enzymatic product, abrogated this effect. Conclusions Early recruitment and alternative activation of macrophages in hypoxic lungs is critical for the later development of HPH. HO-1 may confer protection from HPH by effectively modifing macrophage activation state in hypoxia. PMID:21518986

  6. MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension

    PubMed Central

    Ambler, S. Kelly; Li, Min; Sullivan, Timothy M.; Henry, Lauren N.; Crossno, Joseph T.; Long, Carlin S.; Garrington, Timothy P.; Stenmark, Kurt R.

    2013-01-01

    Pulmonary hypertension (PH) results in pressure overload of the right ventricle (RV) of the heart, initiating pathological RV remodeling and ultimately leading to right heart failure. Substantial research indicates that signaling through the MAPK superfamily mediates pathological cardiac remodeling. These considerations led us to test the hypothesis that the regulatory protein MAPKKK-2 (MEKK2) contributes to RV hypertrophy in hypoxia-induced PH. Transgenic mice with global knockout of MEKK2 (MEKK2?/? mice) and age-matched wild-type (WT) mice were exposed to chronic hypobaric hypoxia (10% O2, 6 wk) and compared with animals under normoxia. Exposure to chronic hypoxia induced PH in WT and MEKK2?/? mice. In response to PH, WT mice showed RV hypertrophy, demonstrated as increased ratio of RV weight to body weight, increased RV wall thickness at diastole, and increased cardiac myocyte size compared with normoxic control animals. In contrast, each of these measures of RV hypertrophy seen in WT mice after chronic hypoxia was attenuated in MEKK2?/? mice. Furthermore, chronic hypoxia elicited altered programs of hypertrophic and inflammatory gene expression consistent with pathological RV remodeling in WT mice; MEKK2 deletion selectively inhibited inflammatory gene expression compared with WT mice. The actions of MEKK2 were mediated in part through regulation of the abundance and phosphorylation of its effector, ERK5. In conclusion, signaling by MEKK2 contributes to RV hypertrophy and altered myocardial inflammatory gene expression in response to hypoxia-induced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy and pathological remodeling in human PH. PMID:23125215

  7. Folic Acid Promotes Recycling of Tetrahydrobiopterin and Protects Against Hypoxia-Induced Pulmonary Hypertension by Recoupling Endothelial Nitric Oxide Synthase

    PubMed Central

    Chalupsky, Karel; Kra?un, Damir; Kanchev, Ivan; Bertram, Katharina

    2015-01-01

    Abstract Aims: Nitric oxide (NO) derived from endothelial NO synthase (eNOS) has been implicated in the adaptive response to hypoxia. An imbalance between 5,6,7,8-tetrahydrobiopterin (BH4) and 7,8-dihydrobiopterin (BH2) can result in eNOS uncoupling and the generation of superoxide instead of NO. Dihydrofolate reductase (DHFR) can recycle BH2 to BH4, leading to eNOS recoupling. However, the role of DHFR and eNOS recoupling in the response to hypoxia is not well understood. We hypothesized that increasing the capacity to recycle BH4 from BH2 would improve NO bioavailability as well as pulmonary vascular remodeling (PVR) and right ventricular hypertrophy (RVH) as indicators of pulmonary hypertension (PH) under hypoxic conditions. Results: In human pulmonary artery endothelial cells and murine pulmonary arteries exposed to hypoxia, eNOS was uncoupled as indicated by reduced superoxide production in the presence of the nitric oxide synthase inhibitor, L-(G)-nitro-L-arginine methyl ester (L-NAME). Concomitantly, NO levels, BH4 availability, and expression of DHFR were diminished under hypoxia. Application of folic acid (FA) restored DHFR levels, NO bioavailability, and BH4 levels under hypoxia. Importantly, FA prevented the development of hypoxia-induced PVR, right ventricular pressure increase, and RVH. Innovation: FA-induced upregulation of DHFR recouples eNOS under hypoxia by improving BH4 recycling, thus preventing hypoxia-induced PH. Conclusion: FA might serve as a novel therapeutic option combating PH. Antioxid. Redox Signal. 23, 1076–1091. PMID:26414244

  8. Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats

    PubMed Central

    Jaarin, Kamsiah; Foong, Wai Dic; Yeoh, Min Hui; Kamarul, Zaman Yusoff Nik; Qodriyah, Haji Mohd Saad; Azman, Abdullah; Zuhair, Japar Sidik Fadhlullah; Juliana, Abdul Hamid; Kamisah, Yusof

    2015-01-01

    OBJECTIVES This study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers. METHODS: Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME (25 mg/kg, intraperitoneally). Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg/kg and Nigella sativa oil at a dose of 2.5 mg/kg for 8 weeks, respectively, concomitantly with L-NAME administration. RESULTS Nigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO. CONCLUSION: The antihypertensive effect of Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension. PMID:26602523

  9. Angiotensin II-Induced Hypertension Is Attenuated by Reduction of Sympathetic Output in NO-Sensitive Guanylyl Cyclase 1 Knockout Mice.

    PubMed

    Broekmans, Kathrin; Stegbauer, Johannes; Potthoff, Sebastian A; Russwurm, Michael; Koesling, Doris; Mergia, Evanthia

    2016-01-01

    In the regulation of vascular tone, the dilatory nitric oxide (NO)/cGMP pathway balances vasoconstriction induced by the renin-angiotensin and sympathetic nervous systems. NO-induced cGMP formation is catalyzed by two guanylyl cyclases (GC), NO-sensitive guanylyl cyclase 1 (NO-GC1) and NO-GC2, with indistinguishable enzymatic properties. In vascular smooth muscle cells, NO-GC1 is the major isoform and is responsible for more than 90% of cGMP formation. Despite reduced vasorelaxation, NO-GC1-deficient mice are not hypertensive. Here, the role of NO-GC1 in hypertension provoked by contractile agonists angiotensin II (Ang II) and norepinephrine (NE) was evaluated in NO-GC1-deficient mice. Hypertension induced by chronic Ang II treatment did not differ between wild-type (WT) and NO-GC1 knockout mice (KO). Also, attenuation of NO-dependent aortic relaxation induced by the Ang II treatment was similar in both genotypes and was most probably attributable to an increase of phosphodiesterase 1 expression. Analysis of plasma NE content-known to be influenced by Ang II-revealed lower NE in the NO-GC1 KO under Ang II-treated- and nontreated conditions. The finding indicates reduced sympathetic output and is underlined by the lower heart rate in the NO-GC1 KO. To find out whether the lack of higher blood pressure in the NO-GC1 KO is a result of reduced sympathetic activity counterbalancing the reduced vascular relaxation, mice were challenged with chronic NE application. As the resulting blood pressure was higher in the NO-GC1 KO than in WT, we conclude that the reduced sympathetic activity in the NO-GC1 KO prevents hypertension and postulate a possible sympatho-excitatory action of NO-GC1 counteracting NO-GC1's dilatory effect in the vasculature. PMID:26559126

  10. The variant N363S of glucocorticoid receptor in steroid-induced ocular hypertension in Hungarian patients treated with photorefractive keratectomy

    PubMed Central

    Borgulya, Gábor; Filkorn, Tamás; Majnik, Judit; Bányász, Ilona; Nagy, Zoltán Zsolt

    2007-01-01

    Purpose Variation in sensitivity to glucocorticoids observed in healthy population is influenced by genetic polymorphisms of the glucocorticoid receptor gene (NR3C1). N363S, ER22/23EK, and Bcl I have been previously described as glucocorticoid-sensitivity modulating polymorphisms. We investigated whether these variants may contribute to steroid-induced ocular hypertension and if they play a role as protective or risk factors during exogenous glucocorticoid administration. Methods We examined 102 patients who underwent photorefractive keratectomy and received topical steroids (either fluorometholone 0.1% or prednisolone acetate 0.5% alone or combined) as part of postoperative therapy. The choice of steroid depended on course of wound healing and regression. Variations in intraocular pressure (IOP) levels in response to steroid therapy were observed. To genotype DNA, allele-specific PCR amplification was applied for the N363S polymorphism, and PCR-based restriction fragment length polymorphism analysis was performed to examine the Bcl I and the ER22/23EK polymorphisms. We separately analyzed data from three groups of patients: those who received fluorometholone only; those who were initially given fluorometholone then later switched to prednisolone acetate; and those who received prednisolone acetate only. Covariance analysis with forward stepwise variable selection was carried out. Results In cases where prednisolone acetate was administered, we found a significant correlation between N363S heterozygosity and steroid-induced ocular hypertension. ER22/23EK and Bcl I polymorphisms do not have a major influence on the risk of developing steroid-induced ocular hypertension. Conclusions Genotyping of high risk steroid responders may allow an individual therapy to avoid steroid-induced ocular hypertension. The N363S polymorphism may have a clinical significance in the future. PMID:17563720

  11. Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy

    NASA Technical Reports Server (NTRS)

    Bartunek, J.; Weinberg, E. O.; Tajima, M.; Rohrbach, S.; Katz, S. E.; Douglas, P. S.; Lorell, B. H.; Schneider, M. (Principal Investigator)

    2000-01-01

    BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

  12. Candidate genes in quantitative trait loci associated with absolute and relative kidney weight in rats with Inherited Stress Induced Arterial Hypertension

    PubMed Central

    2015-01-01

    Background The kidney mass is significantly increased in hypertensive ISIAH rats with Inherited Stress Induced Arterial Hypertension as compared with normotensive WAG rats. The QTL/microarray approach was carried out to determine the positional candidate genes in the QTL for absolute and relative kidney weight. Results Several known and predicted genes differentially expressed in ISIAH and WAG kidney were mapped to genetic loci associated with the absolute and relative kidney weight in 6-month old F2 hybrid (ISIAHxWAG) males. The knowledge-driven filtering of the list of candidates helped to suggest several positional candidate genes, which may be related to the structural and mass changes in hypertensive ISIAH kidney. In the current study, we showed that all loci found for absolute and relative kidney weight didn't overlap with significant or suggestive loci for arterial blood pressure level. So, the genes differentially expressed in ISIAH and WAG kidneys and located in these QTL regions associated with absolute and relative kidney weight shouldn't substantially influence the BP level in the 6 month-old ISIAH rats. However, in some cases, small effects may be suggested. Conclusions The further experimental validation of causative genes and detection of polymorphisms will provide opportunities to advance our understanding of the underlying nature of structural and mass changes in hypertensive ISIAH kidney. PMID:25707311

  13. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO AIRWAY DISEASE INDUCED BY SULFUR DIOXIDE

    EPA Science Inventory

    Rodent models of chronic pulmonary diseases induced by sulfur dioxide (SO2), elastase or tobacco smoke have limited utility because of their lack of chronicity of inflammation, and they demonstrate limited sensitivity to a given experimental manipulation. We hypothesized that dis...

  14. 20-HETE and furosemide-induced natriuresis in salt-sensitive essential hypertension.

    PubMed

    Laffer, Cheryl L; Laniado-Schwartzman, Michal; Wang, Mong-Heng; Nasjletti, Alberto; Elijovich, Fernando

    2003-03-01

    Cyclooxygenase metabolites of arachidonic acid modulate the natriuretic effect of furosemide. It is not known whether 20-HETE, a monooxygenase metabolite of arachidonic acid that also inhibits sodium transport, participates in the action of furosemide. We measured urine sodium (UNaV) and 20-HETE during furosemide diuresis (40 mg three times over 12 hours) in 12 salt-sensitive (SS) and 11 salt-resistant (SR), salt-replete hypertensive subjects (126+/-24 mmol/24 hours positive sodium balance produced by 160-mmol-sodium diet and 2 L saline infusion). Individual systolic blood pressure decreases from the salt-replete to the salt-depleted state were the index of salt-sensitivity. SS had low plasma renin with blunted responses to changes in salt balance, inappropriate plasma aldosterone, and an increased aldosterone/renin ratio. UNaV by furosemide was less in SS (263+/-25 mmol/12 hours) than in SR (351+/-25 mmol/12 hours, P<0.02) patients. 20-HETE was not different between SS and SR patients before (1.92+/-0.38 versus 1.37+/-0.34 microg/h) or after furosemide (1.52+/-0.27 versus 2.01+/-0.40 microg/h), but furosemide changed 20-HETE excretion in opposite direction in SR (0.63+/-0.26) versus SS (-0.40+/-0.17, P<0.005) patients. In all patients together, %Delta20-HETE by furosemide correlated with %DeltaUNaV (r=0.56, P<0.01) and negatively with salt-sensitivity of blood pressure (r=-0.55, P<0.01). In SS, Delta20-HETE by furosemide correlated with Deltaaldosterone/renin ratio (r=0.60, P<0.05), whereas 20-HETE during furosemide had a negative correlation with body mass index (r=-0.73, P<0.01). Our data suggest that 20-HETE modulates the natriuretic response to furosemide, and impaired natriuresis of SS involves a mechanism that alters the 20-HETE response to furosemide and is linked to salt-sensitivity of blood pressure. PMID:12623983

  15. Leptin knockout attenuates hypoxia-induced pulmonary arterial hypertension by inhibiting proliferation of pulmonary arterial smooth muscle cells.

    PubMed

    Chai, SanBao; Wang, Wang; Liu, Jie; Guo, Huan; Zhang, ZhiFei; Wang, Chen; Wang, Jun

    2015-12-01

    Pulmonary arterial hypertension (PAH) is a fatal disease characterized by excessive vascular smooth muscle cells proliferation in small pulmonary arteries, leading to elevation of pulmonary vascular resistance with consequent right ventricular (RV) failure and death. Recently, emerging evidence has shown that leptin signaling is involved in different cardiac pathologies; however, the role of leptin remains limited in the setting of PAH. Thus, in this study, we tested the hypothesis of direct involvement of leptin in the development of PAH. Our data show that leptin activity in plasma and protein level in the lung were higher in hypoxia- and monocrotaline-induced PAH models compared with control animals. Wild-type (WT) and C57BL/6J-Lep(ob) (ob/ob) male mice were exposed to normobaric hypoxia (10% O2) or normoxia (21% O2). After 2 and 4 weeks of chronic hypoxia exposure, WT mice developed PAH as reflected by the increased values of RV systolic pressure, RV hypertrophy index, the medial wall thickness of pulmonary arterioles, and muscularization of pulmonary arterioles. And, all these alterations were attenuated in ob/ob mice treated with hypoxia. Leptin could stimulate the proliferation of pulmonary arterial smooth muscle cells (PASMCs) by activating extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and Akt pathways. These data suggest that the leptin signaling pathway is crucial for the development of PAH. Leptin activates ERK, STAT, and Akt pathways and subsequently PASMCs proliferation, providing new mechanistic information about hypoxia-induced PAH. PMID:26470682

  16. Hypertension in pregnancy: new recommendations for management.

    PubMed

    Shear, R; Leduc, L; Rey, E; Moutquin, J M

    1999-12-01

    Hypertension in pregnancy is a frequent complication that has substantial adverse perinatal outcomes. Hypertension may be preexisting (chronic) essential or secondary hypertension; a second entity is pregnancy induced (gestational hypertension, preeclampsia). Recent advances have identified newer markers for pregnancy hypertension: several potential candidate genes may explain the apparent family inheritance of preeclampsia, and some thrombophilic markers have been associated with the condition. Management options for mild to moderate hypertension include a short hospital stay to exclude ongoing severe hypertension and to ascertain fetal well-being. Outpatient care with appropriate maternal and fetal surveillance, including umbilical artery doppler velocimetry, is recommended for better perinatal outcomes. Acute care for severe hypertension includes the use of magnesium sulfate to prevent eclampsia and antihypertensive medication. Expeditious delivery is recommended when the maternal or fetal states cannot be stabilized. Follow-up after delivery allows the uncovering of any other coexisting hypertensive or cardiovascular disorder. PMID:10981117

  17. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    SciTech Connect

    Kang, Yu-Ming; Zhang, Dong-Mei; Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing; Suo, Yu-Ping; Yue, Li-Ying; Zhu, Guo-Qing; Qin, Da-Nian

    2014-02-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 ?g/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1? and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced hypertension and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced imbalance of PVN neurotransmitters. • PVN inhibition of ACE attenuates ANG II-induced imbalance of cytokines in the PVN. • PVN blockade of AT1-R attenuates ANG II-induced imbalance of cytokines in the PVN.

  18. PARP-Inhibitor Treatment Prevents Hypertension Induced Cardiac Remodeling by Favorable Modulation of Heat Shock Proteins, Akt-1/GSK-3? and Several PKC Isoforms

    PubMed Central

    Deres, Laszlo; Bartha, Eva; Palfi, Anita; Eros, Krisztian; Riba, Adam; Lantos, Janos; Kalai, Tamas; Hideg, Kalman; Sumegi, Balazs; Gallyas, Ferenc; Toth, Kalman; Halmosi, Robert

    2014-01-01

    Spontaneously hypertensive rat (SHR) is a suitable model for studies of the complications of hypertension. It is known that activation of poly(ADP-ribose) polymerase enzyme (PARP) plays an important role in the development of postinfarction as well as long-term hypertension induced heart failure. In this study, we examined whether PARP-inhibitor (L-2286) treatment could prevent the development of hypertensive cardiopathy in SHRs. 6-week-old SHR animals were treated with L-2286 (SHR-L group) or placebo (SHR-C group) for 24 weeks. Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY group). Echocardiography was performed, brain-derived natriuretic peptide (BNP) activity and blood pressure were determined at the end of the study. We detected the extent of fibrotic areas. The amount of heat-shock proteins (Hsps) and the phosphorylation state of Akt-1Ser473, glycogen synthase kinase (GSK)-3?Ser9, forkhead transcription factor (FKHR)Ser256, mitogen activated protein kinases (MAPKs), and protein kinase C (PKC) isoenzymes were monitored. The elevated blood pressure in SHRs was not influenced by PARP-inhibitor treatment. Systolic left ventricular function and BNP activity did not differ among the three groups. L-2286 treatment decreased the marked left ventricular (LV) hypertrophy which was developed in SHRs. Interstitial collagen deposition was also decreased by L-2286 treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2Thr183-Tyr185, Akt-1Ser473, GSK-3?Ser9, FKHRSer256, and PKC ?Ser729 and the level of Hsp90 were increased, while the activity of PKC ?/?IIThr638/641, ?/?410/403 were mitigated by L-2286 administration. We could detect signs of LV hypertrophy without congestive heart failure in SHR groups. This alteration was prevented by PARP inhibition. Our results suggest that PARP-inhibitor treatment has protective effect already in the early stage of hypertensive myocardial remodeling. PMID:25014216

  19. Hypertensive emergencies.

    PubMed

    Feitosa-Filho, Gilson Soares; Lopes, Renato Delascio; Poppi, Nilson Tavares; Guimarães, Hélio Penna

    2008-09-01

    Emergencies and hypertensive crises are clinical situations which may represent more than 25% of all medical emergency care. Considering such high prevalence, physicians should be prepared to correctly identify these crises and differentiate between urgent and emergent hypertension. Approximately 3% of all visits to emergency rooms are due to significant elevation of blood pressure. Across the spectrum of blood systemic arterial pressure, hypertensive emergency is the most critical clinical situation, thus requiring special attention and care. Such patients present with high blood pressure and signs of acute specific target organ damage (such as acute myocardial infarction, unstable angina, acute pulmonary edema, eclampsia, and stroke). Key elements of diagnosis and specific treatment for the different presentations of hypertensive emergency will be reviewed in this article. The MedLine and PubMed databases were searched for pertinent abstracts, using the key words "hypertensive crises" and "hypertensive emergencies". Additional references were obtained from review articles. Available English language clinical trials, retrospective studies and review articles were identified, reviewed and summarized in a simple and practical way. The hypertensive crisis is a clinical situation characterized by acute elevation of blood pressure followed by clinical signs and symptoms. These signs and symptoms may be mild (headache, dizziness, tinnitus) or severe (dyspnea, chest pain, coma or death). If the patient presents with mild symptoms, but without acute specific target organ damage, diagnosis is hypertensive urgency. However, if severe signs and symptoms and acute specific target organ damage are present, then the patient is experiencing a hypertensive emergency. Some patients arrive at the emergency rooms with high blood pressure, but without any other sign or symptom. In these cases, they usually are not taking their medications correctly. Therefore, this is not a hypertensive crisis, but rather non-controlled chronic hypertension. This type of distinction is important for those working in emergency rooms and intensive care unit. Correct diagnosis must be made to assure the most appropriate treatment. PMID:25307099

  20. Erythropoietin-induced hypertensive urgency in a patient with chronic renal insufficiency: case report and review of the literature.

    PubMed

    Novak, Barbara L; Force, Rex W; Mumford, Brett T; Solbrig, Ronald M

    2003-02-01

    Hypertension is a potentially dangerous side effect of erythropoietin treatment; however, extreme elevations in blood pressure are rare. A 75-year-old woman with chronic renal insufficiency was treated with subcutaneous erythropoietin. Three weeks before she started receiving erythropoietin, her hematocrit was 27.2%; after 5 weeks of treatment, it rose to 45.7%. The patient came to the emergency department and was admitted with hypertensive urgency. During her hospital stay she was treated with nitroglycerin and nitroprusside infusions, extended-release nifedipine, a variety of beta-blockers, clonidine, and furosemide. By day 3, her blood pressure was adequately controlled. Her renal insufficiency may have progressed as a result of the hypertensive episode, which probably was related to erythropoietin administration and the resultant rapid increase in her hematocrit. Erythropoietin dosing should be titrated to increase the hematocrit gradually, and blood pressure should be monitored closely to avoid serious side effects such as hypertensive emergencies. PMID:12587817

  1. Effect of hypertension on the structural and functional integrity of the young and aged brain in an inducible transgenic model 

    E-print Network

    Pannozzo, Mercede Alcina

    2014-06-28

    Hypertension has been associated with causing deleterious effects to the cerebrovasculature, which are thought to underlie the formation of white matter lesions (WML) and predispose individuals to age related cognitive ...

  2. Blood Pressure Interventions Affect Acute and Four-Week Diesel Exhaust Induced Pulmonary Injury in Healthy and Hypertensive Rats

    EPA Science Inventory

    Rationale: We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicits changes in cardiac gene expression that broadly mimics expression in spontaneously hypertensive (SH) rats without DE. We hypothesized that pharmacol...

  3. Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats

    PubMed Central

    Husain, Kazim; Ferder, Leon; Ansari, Rais A; Lalla, Jainarine

    2015-01-01

    The study aim was to investigate the relationship of chronic ethanol-induced inflammation leading to vascular endothelial injury and elevation of blood pressure (BP) in a rat model. Male Fisher rats were divided into two groups of six animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) 20% ethanol (4 g kg ?1, orally) daily for 12 weeks. The mean arterial blood pressure was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; thoracic aorta were isolated and analyzed for aortic reactivity response, inflammatory mediators, oxidant/antioxidant enzyme protein expression and endothelial nitric oxide-generating system. The results show that the mean BP was significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to increased aortic inflammation (tumor necrosis factor [TNF]-?; nitric oxide synthase [iNOS], COX-2 and MCP-1 protein expression) and elevated angiotensin II levels in alcohol-treated group compared to control. Aortic Nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity, membrane and cytosolic subunits p22phox and p47phox expression and Mn-SOD activity and protein expression significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF)-A and CuZn-SOD activity and protein expression significantly decreased in alcohol-treated group compared to control. The acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol-treated rats compared to control. In conclusion, chronic ethanol-induced elevation in BP is related to increased aortic inflammation, elevated angiotensin II levels, induction of NADPH oxidase causing endothelial injury, depletion of CuZn-SOD, down-regulation of endothelial NO generating system and impaired vascular relaxation in rats. PMID:20921064

  4. Salt-Sensitive Hypertension Induced by Decoy of Transcription Factor HIF-1? in the Renal Medulla

    PubMed Central

    Li, Ningjun; Li, Chen; Yi, Fan; Xia, Min; Li, Pin-Lan

    2009-01-01

    Hypoxia inducible factor-1? (HIF-1?), a transcription factor, is abundantly expressed in the renal medulla and regulates many oxygen-sensitive genes such as nitric oxide synthase (NOS), cyclooxygenase-2 and heme oxygenase-1 (HO-1). Given the important roles of these genes in the control of arterial pressure, the present study was to test the hypothesis that HIF-1?-mediated gene activation serves as an antihypertensive pathway by regulating renal medullary function and sodium excretion. HIF-1? decoy oligodeoxynucleotides (ODN) or scrambled ODN were transfected into the renal medulla in uninephretomized Sprague Dawley rats. Two weeks after ODN transfection, the HIF-1? binding activities were significantly inhibited by 45%, and high salt-induced increases of NOS2 and HO-1 transcriptions were also inhibited by 70% and 61% in the renal medulla from decoy rats. The natriuretic responses and increases of renal medullary blood flow (MBF) responding to the elevations of renal perfusion pressure were significantly blunted by 50% and 37% in decoy rats. Intravenously acute sodium loading increased MBF and urinary sodium excretion, which was remarkably attenuated in decoy rats. In decoy rats, high salt intake caused a greater positive sodium balance. Consequently, arterial pressure was remarkably increased (from 118 ± 1.9 to 154 ± 6.3 mmHg) in decoy rats, but not in control rats, when the rats were challenged with a high salt diet. There was no blood pressure change in decoy rats that were maintained in normal salt diet. In conclusion, HIF-1?-mediated gene activation importantly participates in the regulation of renal medullary function and long-term arterial blood pressure. PMID:18356541

  5. Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats.

    PubMed

    Arima, Shiho; Uto, Hirofumi; Ibusuki, Rie; Kumamoto, Ryo; Tanoue, Shirou; Mawatari, Seiichi; Oda, Kohei; Numata, Masatsugu; Fujita, Hiroshi; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito

    2014-01-01

    The effect of hypertension on non-alcoholic fatty liver disease (NAFLD) remains unclear at the molecular level. In this study, we investigated the effects of hypertension on the degree of hepatic steatosis, liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined (CDAA) diet in spontaneously hypertensive rats (SHRs). Seven-week-old male SHRs were fed standard chow with high or normal salt concentrations for 7 weeks, followed by a CDAA diet containing high or normal salt for an additional 8 or 24 weeks. Hepatic steatosis was assessed using hepatic triglyceride levels and Oil red O staining. Hepatic fibrosis was evaluated using Sirius red and Azan staining. Systolic blood pressure (SBP) gradually increased with a high-salt diet and was significantly higher after 7 weeks of feeding with high-salt vs. normal-salt chow. After 8 weeks on the CDAA diet, the degree of hepatic steatosis did not differ between the high-salt and normal-salt groups; however, alanine aminotransferase and fasting blood glucose levels were significantly higher and hepatic mRNA levels for interleukin (IL)-10 and heme oxygenase (HO)-1 were significantly lower in the high-salt group compared with the normal-salt group. After 24 weeks on the CDAA diet, the high-salt group had significantly more severe hepatic fibrosis and a higher hepatic mRNA expression of ?-smooth muscle actin and lower hepatic IL-10 and HO-1 mRNA levels compared with the normal-salt group. In conclusion, our results indicate that hypertension is a potential risk factor for liver injury and hepatic fibrosis through glucose intolerance and decreased IL-10-mediated or HO-1-induced anti-inflammatory mechanisms. PMID:24190226

  6. The Anti-hypertensive Drug Prazosin Induces Apoptosis in the Medullary Thyroid Carcinoma Cell Line TT

    PubMed Central

    STRACKE, ANIKA; MEIER-ALLARD, NATHALIE; ABSENGER, MARKUS; INGOLIC, ELISABETH; HAAS, HELGA SUSANNE; PFRAGNER, ROSWITHA; SADJAK, ANTON

    2015-01-01

    Background/Aim Medullary thyroid carcinoma (MTC) is a tumor associated with poor prognosis since it exhibits high resistance against conventional cancer therapy. Recent studies have shown that quinazolines exhibit a pro-apoptotic effect on malignant cells. The aim of the present study was to elucidate whether MTC cells are affected by quinazolines, in particular prazosin. Materials and Methods Proliferation, apoptosis and cell morphology of the MTC cell line TT were analyzed by WST-1 assay, caspase 3/7 activation tests and microscopy. Fibroblasts were used as control for non-malignant cells. Results Prazosin potently inhibited the growth of TT cells, induced apoptosis and caused vacuolization, as well as needle-like filopodia. Fibroblasts were affected by prazosin in the same way as MTC cells. Conclusion MTC cells are responsive to prazosin treatment similar to other malignancies. The fact that fibroblasts also respond to prazosin further highlights the importance to identify the unknown pro-apoptotic target of quinazolines. PMID:25550532

  7. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines.

    PubMed

    Kang, Yu-Ming; Zhang, Dong-Mei; Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing; Suo, Yu-Ping; Yue, Li-Ying; Zhu, Guo-Qing; Qin, Da-Nian

    2014-02-01

    The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5?g/h) or vehicle for 4weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1? and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. PMID:24342267

  8. http://pih.sagepub.com/ Engineers, Part H: Journal of Engineering in

    E-print Network

    Vaziri, Ashkan

    investigation of load- induced structure remodeling in the proximal femur Ali Marzban1 , Paul Canavan2,3 , Grant, Grant Warner, Ashkan Vaziri and Hamid Nayeb-Hashimi Parametric investigation of load-induced structure remodeling in the proximal femur Published by: http://www.sagepublications.com On behalf of: Institution

  9. Impact of tannic acid on blood pressure, oxidative stress and urinary parameters in L-NNA-induced hypertensive rats.

    PubMed

    Turgut Co?an, Didem; Saydam, Faruk; Özbayer, Cansu; Do?aner, Fulya; Soyocak, Ahu; Güne?, Hasan Veysi; De?irmenci, ?rfan; Kurt, Hülyam; Üstüner, Mehmet Cengiz; Bal, Cengiz

    2015-01-01

    Hypertension is a major health problem with increasing prevalence around the world. Tannic acid is water-soluble polyphenol that is present in tea, green tea, coffee, red wine, nuts, fruits and many plant foods. It has been reported to serve as an antioxidant or a pro-oxidant depending on the type of cells and its concentration. The purpose of our study was to evaluate the effect of tannic acid on systolic blood pressure, oxidative stress and some urinary parameters in the rat model of essential hypertension. Blood pressures of all rats were measured using the tail-cuff method. The nitric oxide synthase inhibitor N (omega)-nitro-L-arginine was administered orally at a dose of 0.5 g/l/day for 15 days to rats in order to create an animal model of hypertension. Tannic acid was intraperitoneally injected at a dose of 50 mg/kg for 15 days. Superoxide dismutase, catalase activity and the concentration of malondialdehyde (MDA) were determined in blood plasma and homogenates of heart, liver and kidney. In order to evaluate renal functions, urine pH, urine volume, urine creatine, uric acid, and urea nitrogen values were measured. Compared with the hypertension group, a decrease in MDA concentrations of heart tissue (p < 0.01), urea nitrogen values (p < 0.01) and urine volumes (p < 0.001) were established in hypertension + tannic acid group. There was also a decrease in blood pressure values (20th and 30th days) of this group, but there was no a statistical difference according to hypertension group. The findings of our research show the effect of tannic acid in lowering blood pressure in hypertensive rats. PMID:24306272

  10. The value of the mean arterial blood pressure in the second trimester (MAP-2 value) as a predictor of pregnancy-induced hypertension and preeclampsia. A preliminary report.

    PubMed

    Oney, T; Kaulhausen, H

    1983-01-01

    In 200 healthy nulliparous women the mean arterial blood pressure in the second trimester (MAP-2 value) was calculated. 85 women (42 %) had a MAP-2 value of greater than or equal to 90 mmHg (positive test result), but only 27 women (32 %) developed a hypertensive complication. Conversely, 113 of the 115 (98 %) women with a negative test result (MAP-2 value less than 90 mmHg) remained normotensive. Only two women of this group (2 %) later showed a mild pregnancy-induced hypertension. Thus, the MAP-2 value has a high sensitivity (93 %) and a high predictive value of negative test results (98 %). On the other hand, there is a high rate of false-positive results (68 %) and thus a low predictive value of positive test results (32 %). It is concluded that the MAP-2 value is a simple method for selecting pregnant women who should be examined with other more specific predictive tests. Alternatively, weekly measurements of blood pressure are recommended for early diagnosis of hypertensive disorders of late pregnancy in all women with a MAP-2 value of 90 mmHg or more. PMID:6872284

  11. Hypertensive disorders of pregnancy.

    PubMed

    Doan-Wiggins, L

    1987-08-01

    Pre-eclampsia/eclampsia, or pregnancy-induced hypertension, is an uncommon but life-threatening complication of pregnancy associated with significant perinatal morbidity. When superimposed on underlying chronic hypertension, its impact on the fetus becomes even greater. Although the pathophysiology of the disease has not been fully defined, vasospasm appears to be the principal, underlying, etiologic mechanism. Therapy of the disease is principally aimed at controlling convulsions with magnesium sulfate and controlling hypertension with the antihypertensive agent hydralazine. Because development of the disease depends on the presence of trophoblastic tissue, the only true cure for pre-eclampsia/eclampsia is removal of the trophoblast through delivery of the infant. The timing and type of delivery is dependent on the severity of the disease and gestational age of the infant. PMID:3308427

  12. The effect of hydroalcoholic extract from the leaves of Moringa peregrina (Forssk.) Fiori. on blood pressure and oxidative status in dexamethasone-induced hypertensive rats

    PubMed Central

    Safaeian, Leila; Asghari, Gholamreza; Javanmard, Shaghayegh Haghjoo; Heidarinejad, Arman

    2015-01-01

    Background: Moringa peregrina (Forssk.) Fiori. is a tropical tree growing in southeast of Iran. All parts of this plant have nutritional uses and pharmacological activities. The present study was designed to evaluate the effect of hydroalcoholic extract from the leaves of M. peregrina in dexamethasone (Dex)-induced hypertension in rats. Materials and Methods: Male Wistar rats received Dex (30 ?g/kg, subcutaneously; s.c.) or saline (as vehicle, 1 ml/kg, s.c.) for 14 days. In a prevention study, the rats received M. peregrina extract (100, 200 and 400 mg/kg, orally) for 4 days, followed by Dex for 14 days. In a reversal study, the animals received M. peregrina extract orally from day 8 to 14. The systolic blood pressure (SBP) was measured using tail-cuff method. The hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) were assessed in plasma samples. Results: Dex significantly increased the SBP and the plasma H2O2 and decreased the plasma FRAP value (P < 0.001). M. peregrina extract at a dose of 400 mg/kg prevented (P < 0.01) but did not reverse Dex-induced hypertension in rats. It also dose-dependently reduced the plasma H2O2 concentration and improved the FRAP value upon Dex administration. Conclusions: The findings of the present study indicated the antioxidant and partially antihypertensive effects of the hydroalcoholic extract from the leaves of M. peregrina in Dex-induced hypertension. Further experiments on other fractions of the leaves and also other parts of this plant are suggested for better evaluation of its antihypertensive effect and finding its mechanisms of action. PMID:26015927

  13. Gene expression of cyclin-dependent kinase inhibitors and effect of heparin on their expression in mice with hypoxia-induced pulmonary hypertension

    SciTech Connect

    Yu Lunyin; Quinn, Deborah A.; Garg, Hari G.; Hales, Charles A. . E-mail: chales@partners.org

    2006-07-14

    The balance between cell proliferation and cell quiescence is regulated delicately by a variety of mediators, in which cyclin-dependent kinases (CDK) and CDK inhibitors (CDKI) play a very important role. Heparin which inhibits pulmonary artery smooth muscle cell (PASMC) proliferation increases the levels of two CDKIs, p21 and p27, although only p27 is important in inhibition of PASMC growth in vitro and in vivo. In the present study we investigated the expression profile of all the cell cycle regulating genes, including all seven CDKIs (p21, p27, p57, p15, p16, p18, and p19), in the lungs of mice with hypoxia-induced pulmonary hypertension. A cell cycle pathway specific gene microarray was used to profile the 96 genes involved in cell cycle regulation. We also observed the effect of heparin on gene expression. We found that (a) hypoxic exposure for two weeks significantly inhibited p27 expression and stimulated p18 activity, showing a 98% decrease in p27 and 81% increase in p18; (b) other CDKIs, p21, p57, p15, p16, and p19 were not affected significantly in response to hypoxia; (c) heparin treatment restored p27 expression, but did not influence p18; (d) ERK1/2 and p38 were mediators in heparin upregulation of p27. This study provides an expression profile of cell cycle regulating genes under hypoxia in mice with hypoxia-induced pulmonary hypertension and strengthens the previous finding that p27 is the only CDKI involved in heparin regulation of PASMC proliferation and hypoxia-induced pulmonary hypertension.

  14. Hypertension screening

    NASA Technical Reports Server (NTRS)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  15. Renovascular hypertension

    MedlinePLUS

    ... and diagnosis. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook ... hypertension: Therapy. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook ...

  16. Pulmonary Hypertension

    MedlinePLUS

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  17. Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat

    PubMed Central

    Collister, John P.; Bellrichard, Mitch; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C.

    2014-01-01

    The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·?) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·? in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·? in the MnPO contributes to the development of chronic AngII-dependent hypertension. PMID:25474089

  18. Persistent perioperative tachycardia and hypertension diagnosed as thyroid storm induced by a hydatidiform mole: a case report.

    PubMed

    Hwang, Wonjung; Im, Daehwan; Kim, Eunsung

    2014-09-01

    Thyroid storm is a critical complication of molar pregnancy. However, early diagnosis of it is difficult because it is a rare complication and usually presents nonspecific findings. In this case report, we present a woman with molar pregnancy who had persistent tachycardia and hypertension. She was diagnosed initially with preeclampsia and sepsis as complications of molar pregnancy. During dilation and curettage under general anesthesia with sevoflurane and remifentanil, tachycardia and hypertension remained even with continuous infusion of labetalol. The patient was subsequently diagnosed with thyroid storm associated with molar pregnancy. She was restored to a clinically euthyroid state 1 day after the operation, and her thyroid function test and ?-hCG values were normal 3 months later. The anesthesiologists should bear in mind the possibility of thyroid storm in patients with molar pregnancies who show persistent tachycardia and hypertension. PMID:25302097

  19. Increased reactive oxygen species, metabolic maladaptation, and autophagy contribute to pulmonary arterial hypertension-induced ventricular hypertrophy and diastolic heart failure.

    PubMed

    Rawat, Dhawjbahadur K; Alzoubi, Abdallah; Gupte, Rakhee; Chettimada, Sukrutha; Watanabe, Makino; Kahn, Andrea G; Okada, Takao; McMurtry, Ivan F; Gupte, Sachin A

    2014-12-01

    Pulmonary arterial hypertension (PAH) is a debilitating and deadly disease with no known cure. Heart failure is a major comorbidity and a common cause of the premature death of patients with PAH. Increased asymmetrical right ventricular hypertrophy and septal wall thickening compress the left ventricular cavity and elicit diastolic heart failure. In this study, we used the Sugen5416/hypoxia/normoxia-induced PAH rat to determine whether altered pyridine nucleotide signaling in the failing heart contributes to 1) increased oxidative stress, 2) changes in metabolic phenotype, 3) autophagy, and 4) the PAH-induced failure. We found that increased reactive oxygen species, metabolic maladaptation, and autophagy contributed to the pathogenesis of right ventricular remodeling and hypertrophy that lead to left ventricular diastolic dysfunction. In addition, arterial elastance increased in PAH rats. Glucose-6-phosphate dehydrogenase is a major source of pyridine molecule (nicotinamide adenine dinucleotide phosphate), which is a substrate for nicotinamide adenine dinucleotide phosphate oxidases in the heart. Dehydroepiandrosterone, a 17-ketosteroid that reduces pulmonary hypertension and right ventricular hypertrophy, inhibited glucose-6-phosphate dehydrogenase, decreased oxidative stress, increased glucose oxidation and acetyl-coA, and reduced autophagy in the hearts of PAH rats. It also decreased arterial stiffness and improved left ventricular diastolic function. These findings demonstrate that pyridine nucleotide signaling, at least partly, mediates PAH-induced diastolic heart failure, and that reduction of glucose-6-phosphate dehydrogenase-derived nicotinamide adenine dinucleotide phosphate is beneficial to improve left ventricle diastolic function. PMID:25267798

  20. [Hypertensive disorders in pregnancy].

    PubMed

    Dürig, P; Ferrier, C; Schneider, H

    1999-10-01

    Hypertension in pregnancy is defined by a systolic blood pressure > or = 140 mm Hg and a diastolic blood pressure of > or = 90 mm Hg or by a rise in blood pressure of systolic > or = 30 mm Hg and diastolic > or = 15 mm Hg. High blood pressures are found in 5-10% of all pregnancies. The outcome of pregnancy is influenced by the fact whether there occurs a proteinuria in addition to hypertension. While the prognosis of an isolated hypotension is good, the combination of hypertension and proteinuria leading to preeclampsia is the primary cause of maternal death in many countries and is responsible for 20-25% of perinatal mortality. A simple classification divides between chronic hypertension, preeclampsia, preeclampsia superimposed on chronic hypertension and transient hypertension. With chronic hypertension pregnancy outcome is determined by a preexisting nephropathy and the occurrence of a superimposed preeclampsia. Preeclampsia and superimposed preeclampsia are pregnancy induced multiorganic diseases, endangering both the mother and the fetus. Transient hypertension is a benign pathology, which occurs toward the end of pregnancy usually on the basis of a latent essential hypertension, which is laid open through pregnancy. While a severe chronic hypertension in pregnancy must be treated to prevent a hypertensive maternal encephalopathy, a less severe chronic hypertension should not be treated as the risk of a superimposed preeclampsia and the maternal and fetal outcome cannot be influenced by antihypertensive therapy. The incidence of preeclampsia is 3-5% in nulliparae and 0.5% in multiparae. Preeclampsia is a severe and dangerous pathology with an unknown etiology. Pregnancy termination is the only causal therapy. At present it is still recommended to terminate a severe preeclampsia after stabilizing the mother, irrespective of gestational age. In less severe preeclampsia occurring before 32 weeks of gestation, termination of pregnancy can be postponed under intensive monitoring and a prophylaxis with magnesium sulfate in order to accelerate the fetal lung maturation with glucocorticoids. A conservative management in the case of a HELLP-syndrome (Haemolyis, Elevated Liver enzymes, Low Platelets), which is a very severe form of preeclampsia, is not recommended because it hasn't been validated in prospective controlled studies. The most dangerous complication of preeclampsia is eclampsia, which is defined by general tonic-clonic convulsions before or after birth. The most effective prophylaxis of eclamptic attacks is the intravenous therapy with magnesium sulfate. A primary prohylaxis for preeclampsia doesn't exist. Treatment with low-dose aspirin in high-risk patients, i.e. after a severe preeclampsia, in cases of chronic hypertension, in cases of nephropathy and in cases with antiphospholipid-syndrome++ can be recommended. The prophylactic use of low-dose heparin, which has lead to a significant decreased incidence of preeclampsia in retrospective analysis, is now the object of a randomized, controlled trial in our hospital. All women who suffered from a preeclampsia should have a check-up after 3-6 months. Preexisting pathologies are found in up to 40% of patients, mostly in multiparae, i.e. chronic hypertension, nephropathy, endocrine pathologies, anomalies of blood coagulation and antiphospolipid-syndrome. PMID:10549228

  1. Beneficial effects of a novel agonist of the adenosine A2A receptor on monocrotaline-induced pulmonary hypertension in rats

    PubMed Central

    Alencar, Allan K N; Pereira, Sharlene L; Montagnoli, Tadeu L; Maia, Rodolfo C; Kümmerle, Arthur E; Landgraf, Sharon S; Caruso-Neves, Celso; Ferraz, Emanuelle B; Tesch, Roberta; Nascimento, José H M; de Sant'Anna, Carlos M R; Fraga, Carlos A M; Barreiro, Eliezer J; Sudo, Roberto T; Zapata-Sudo, Gisele

    2013-01-01

    Background and Purpose Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASSBio-1359), on monocrotaline (MCT)-induced pulmonary hypertension in rats. Experimental Approach PAH was induced in male Wistar rats by a single i.p. injection of MCT (60 mg·kg?1) and 2 weeks later, oral LASSBio-1359 (50 mg·kg?1) or vehicle was given once daily for 14 days. Echocardiography was used to measure cardiac function and pulmonary artery dimensions, with histological assay of vascular collagen. Studies of binding to human recombinant adenosine receptors (A1, A2A, A3) and of docking with A2A receptors were also performed. Key Results MCT administration induced changes in vascular and ventricular structure and function, characteristic of PAH. These changes were reversed by treatment with LASSBio-1359. MCT also induced endothelial dysfunction in pulmonary artery, as measured by diminished relaxation of pre-contracted arterial rings, and this dysfunction was reversed by LASSBio-1359. In pulmonary artery rings from normal Wistar rats, LASSBio-1359 induced relaxation, which was decreased by the adenosine A2A receptor antagonist, ZM 241385. In adenosine receptor binding studies, LASSBio-1359 showed most affinity for the A2A receptor and in the docking analyses, binding modes of LASSBio-1359 and the A2A receptor agonist, CGS21680, were very similar. Conclusion and Implications In rats with MCT-induced PAH, structural and functional changes in heart and pulmonary artery were reversed by treatment with oral LASSBio-1359, most probably through the activation of adenosine A2A receptors. PMID:23530610

  2. The effects of vasoactivity and hypoxic pulmonary hypertension on extralobar pulmonary artery biomechanics

    E-print Network

    Chesler, Naomi C.

    The effects of vasoactivity and hypoxic pulmonary hypertension on extralobar pulmonary artery mortality. Hypoxia- induced pulmonary hypertension (HPH) has been shown to decrease extralobar pulmonary to slowing the progression of right ventricular dysfunction in pulmonary hypertension. Vascular smooth muscle

  3. Role of the Renin-Angiotensin System, Renal Sympathetic Nerve System, and Oxidative Stress in Chronic Foot Shock-Induced Hypertension in Rats

    PubMed Central

    Dong, Tao; Chen, Jing-Wei; Tian, Li-Li; Wang, Lin-Hui; Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Zhao, Xiao-Dong; Zhu, Wei; Wang, Guo-Qing; Sun, Wan-Ping; Zhang, Guo-Xing

    2015-01-01

    Objective: The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension. Methods: Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus. Results: The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril. Conclusions: RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension. PMID:25999788

  4. Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice

    PubMed Central

    Rajapakse, Niwanthi W.; Karim, Florian; Evans, Roger G.

    2015-01-01

    Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1) can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS) on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13) and CAT1 overexpressing mice (CAT+; n=13) were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP) and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p.) on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%). The depressor response to pentolinium was 65% greater in obese WT than lean WT (P < 0.001), but was similar in obese and lean CAT+ (P = 0.65). In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ? 0.001). Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ? 0.001), but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%), but greater in obese CAT+ (37 ± 2%), when compared to respective lean WT (31 ± 3%) and lean CAT+ controls (27 ± 2%; P ? 0.02). We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress. PMID:26186712

  5. Role of the Na+/H+ exchanger 3 in angiotensin II-induced hypertension in NHE3-deficient mice with transgenic rescue of NHE3 in small intestines

    PubMed Central

    Li, Xiao C; Shull, Gary E; Miguel-Qin, Elisa; Chen, Fang; Zhuo, Jia L

    2015-01-01

    The role of Na+/H+ exchanger 3 (NHE3) in the kidney in angiotensin II (ANG II)-induced hypertension remains unknown. The present study used global NHE3-deficient mice with transgenic rescue of the Nhe3 gene in small intestines (tgNhe3?/?) to test the hypothesis that genetic deletion of NHE3 selectively in the kidney attenuates ANG II-induced hypertension. Six groups of wild-type (tgNhe3+/+) and tgNhe3?/? mice were infused with either vehicle or ANG II (1.5 mg/kg/day, i.p., 2 weeks, or 10 nmol/min, i.v., 30 min), treated with or without losartan (20 mg/kg/day, p.o.) for 2 weeks. Basal systolic blood pressure (SBP) and mean intra-arterial blood pressure (MAP) were significantly lower in tgNhe3?/? mice (P < 0.01). Basal glomerular filtration rate, 24 h urine excretion, urinary Na+ excretion, urinary K+ excretion, and urinary Cl? excretion were significantly lower in tgNhe3?/? mice (P < 0.01). These responses were associated with significantly elevated plasma ANG II and aldosterone levels, and marked upregulation in aquaporin 1, the Na+/HCO3 cotransporter, the ?1 subunit isoform of Na+/K+-ATPase, protein kinase C?, MAP kinases ERK1/2, and glycogen synthase kinase 3 ?/? in the renal cortex of tgNhe3?/? mice (P < 0.01). ANG II infusion markedly increased SBP and MAP and renal cortical transporter and signaling proteins in tgNhe3+/+, as expected, but all of these responses to ANG II were attenuated in tgNhe3?/? mice (P < 0.01). These results suggest that NHE3 in the kidney is necessary for maintaining normal blood pressure and fully developing ANG II-dependent hypertension. PMID:26564064

  6. HIV and Pulmonary Hypertension

    MedlinePLUS

    HIV Pulmonary & PH Hypertension Did you know that if you are HIV-positive, you are at risk for pulmonary hypertension? www.PHAssociation.org About Pulmonary Hypertension PULMONARY HYPERTENSION, OR PH, is complex and often misunderstood. PH means high ...

  7. Hypertension and Spina Bifida

    MedlinePLUS

    Hypertension What is hypertension? Hypertension, also called high blood pressure , is a condition in which the arteries of the body have too much ... 60% do not. What are the causes of hypertension in Spina Bil da? It is unclear whether ...

  8. Diagnosing hypertension

    PubMed Central

    Gelfer, Mark; Dawes, Martin; Kaczorowski, Janusz; Padwal, Raj; Cloutier, Lyne

    2015-01-01

    Abstract Objective To highlight the 2015 Canadian Hypertension Education Program (CHEP) recommendations for the diagnosis and assessment of hypertension. Quality of evidence A systematic search was performed current to August 2014 by a Cochrane Collaboration librarian using the MEDLINE and PubMed databases. The search results were critically appraised by the CHEP subcommittee on blood pressure (BP) measurement and diagnosis, and evidence-based recommendations were presented to the CHEP Central Review Committee for independent review and grading. Finally, the findings and recommendations were presented to the Recommendations Task Force for discussion, debate, approval, and voting. The main recommendations are based on level II evidence. Main message Based on the most recent evidence, CHEP has made 4 recommendations in 2 broad categories for 2015 to improve BP measurement and the way hypertension is diagnosed. A strong recommendation is made to use electronic BP measurement in the office setting to replace auscultatory BP measurement. For patients with elevated office readings, CHEP is recommending early use of out-of-office BP measurement, preferably ambulatory BP measurement, in order to identify early in the process those patients with white-coat hypertension. Conclusion Improvements in diagnostic accuracy are critical to optimizing hypertension management in Canada. The annual updates provided by CHEP ensure that practitioners have up-to-date evidence-based information to inform practice. PMID:26564654

  9. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

    PubMed Central

    Berkban, Thewarid; Boonprom, Pattanapong; Bunbupha, Sarawoot; Umka Welbat, Jariya; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Pakdeechote, Poungrat; Prachaney, Parichat

    2015-01-01

    The effect of ellagic acid on oxidative stress and hypertension induced by N?-Nitro-l-arginine methyl ester hydrochloride (L-NAME) was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day) for five weeks. L-NAME induced high systolic blood pressure (SBP) and increased heart rate (HR), hindlimb vascular resistance (HVR) and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg) prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability. PMID:26133972

  10. Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N. S.; Salleh, Md Salzihan Md; Gurtu, Sunil

    2011-01-01

    Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress. PMID:21673929

  11. Exercise Hypertension

    PubMed Central

    Schultz, Martin G.; Sharman, James E.

    2014-01-01

    Irrespective of apparent ‘normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ?210 mm Hg in men or ?190 mm Hg in women or diastolic BP ?110 mm Hg in men or women), a condition termed exercise hypertension or a ‘hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory ‘masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE.

  12. Interleukin 13– and interleukin 17A–induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution

    PubMed Central

    Park, Sung-Hyun; Chen, Wen-Chi; Esmaeil, Nafiseh; Lucas, Benjamin; Marsh, Leigh M.; Reibman, Joan

    2014-01-01

    Abstract Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule ?. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response–induced pulmonary hypertension. PMID:25610601

  13. Portal hypertension induced by congenital hepatic arterioportal fistula: Report of four clinical cases and review of the literature

    PubMed Central

    Zhang, Dan-Ying; Weng, Shu-Qiang; Dong, Ling; Shen, Xi-Zhong; Qu, Xu-Dong

    2015-01-01

    Intrahepatic arterioportal fistula (IAPF) can be caused by many secondary factors. We report four cases of portal hypertension that were eventually determined to be caused by congenital hepatic arterioportal fistula. The clinical manifestations included ascites, variceal hemorrhage and hepatic encephalopathy. Computed tomography scans from all of the patients revealed the early enhancement of the portal branches in the hepatic arterial phase. All patients were diagnosed using digital subtraction angiography (DSA). DSA before embolization revealed an arteriovenous fistula with immediate filling of the portal venous radicles. All four patients were treated with interventional embolization. The four patients remained in good condition throughout follow-up and at the time of publication. IAPF is frequently misdiagnosed due to its rarity; therefore, clinicians should consider IAPF as a potential cause of non-cirrhotic portal hypertension. PMID:25717263

  14. Uncoupling Protein-2 Mediates DPP-4 Inhibitor-Induced Restoration of Endothelial Function in Hypertension Through Reducing Oxidative Stress

    PubMed Central

    Liu, Limei; Liu, Jian; Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Xu, Aimin; Xu, Gang; Ng, Chi Fai; Yao, Xiaoqiang; Gao, Yuansheng

    2014-01-01

    Abstract Aims: Although uncoupling protein 2 (UCP2) negatively regulates intracellular reactive oxygen species (ROS) production and protects vascular function, its participation in vascular benefits of drugs used to treat cardiometabolic diseases is largely unknown. This study investigated whether UCP2 and associated oxidative stress reduction contribute to the improvement of endothelial function by a dipeptidyl peptidase-4 inhibitor, sitagliptin, in hypertension. Results: Pharmacological inhibition of cyclooxygenase-2 (COX-2) but not COX-1 prevented endothelial dysfunction, and ROS scavengers reduced COX-2 mRNA and protein expression in spontaneously hypertensive rats (SHR) renal arteries. Angiotensin II (Ang II) evoked endothelium-dependent contractions (EDCs) in C57BL/6 and UCP2 knockout (UCP2KO) mouse aortae. Chronic sitagliptin administration attenuated EDCs in SHR arteries and Ang II-infused C57BL/6 mouse aortae and eliminated ROS overproduction in SHR arteries, which were reversed by glucagon-like peptide 1 receptor (GLP-1R) antagonist exendin 9-39, AMP-activated protein kinase (AMPK)? inhibitor compound C, and UCP2 inhibitor genipin. By contrast, sitagliptin unaffected EDCs in Ang II-infused UCP2KO mice. Sitagliptin increased AMPK? phosphorylation, upregulated UCP2, and downregulated COX-2 expression in arteries from SHR and Ang II-infused C57BL/6 mice. Importantly, exendin 9-39, compound C, and genipin reversed the inhibitory effect of GLP-1R agonist exendin-4 on Ang II-stimulated mitochondrial ROS rises in SHR endothelial cells. Moreover, exendin-4 improved the endothelial function of renal arteries from SHR and hypertensive patients. Innovation: We elucidate for the first time that UCP2 serves as an important signal molecule in endothelial protection conferred by GLP-1-related agents. UCP2 could be a useful target in treating hypertension-related vascular events. Conclusions: UCP2 inhibits oxidative stress and downregulates COX-2 expression through GLP-1/GLP-1R/AMPK? cascade. Antioxid. Redox Signal. 21, 1571–1581. PMID:24328731

  15. Immunization with an ApoB-100 Related Peptide Vaccine Attenuates Angiotensin-II Induced Hypertension and Renal Fibrosis in Mice

    PubMed Central

    Honjo, Tomoyuki; Chyu, Kuang-Yuh; Dimayuga, Paul C.; Lio, Wai Man; Yano, Juliana; Trinidad, Portia; Zhao, Xiaoning; Zhou, Jianchang; Cercek, Bojan; Shah, Prediman K.

    2015-01-01

    Recent studies suggest the potential involvement of CD8+ T cells in the pathogenesis of murine hypertension. We recently reported that immunization with apoB-100 related peptide, p210, modified CD8+ T cell function in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we hypothesized that p210 vaccine modulates blood pressure in AngII-infused apoE (-/-) mice. Male apoE (-/-) mice were immunized with p210 vaccine and compared to unimmunized controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII for 4 weeks. At 13 weeks of age, p210 immunized mice showed significantly lower blood pressure response to AngII compared to controls. CD8+ T cells from p210 immunized mice displayed a different phenotype compared to CD8+ T cells from unimmunized controls. Serum creatinine and urine albumin to creatinine ratio were significantly decreased in p210 immunized mice suggesting that p210 vaccine had renal protective effect. At euthanasia, inflammatory genes IL-6, TNF-?, and MCP-1 in renal tissue were down-regulated by p210 vaccine. Renal fibrosis and pro-fibrotic gene expression were also significantly reduced in p210 immunized mice. To assess the role of CD8+ T cells in these beneficial effects of p210 vaccine, CD8+ T cells were depleted by CD8 depleting antibody in p210 immunized mice. p210 immunized mice with CD8+ T cell depletion developed higher blood pressure compared to mice receiving isotype control. Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to controls. We conclude that immunization with p210 vaccine attenuated AngII-induced hypertension and renal fibrosis. CD8+ T cells modulated by p210 vaccine could play an important role in the anti-hypertensive, anti-fibrotic and renal-protective effect of p210 vaccine. PMID:26121471

  16. Pulmonary Hypertension

    MedlinePLUS

    ... pressure." Pulmonary hypertension is an increase in blood pressure in the blood vessels that carry blood to the lungs. It is ... the narrowed arteries. This results in high blood pressure in the right side of your heart and in the blood vessels that carry blood to the lungs. Symptoms What ...

  17. Regulation of soluble guanylyl cyclase-?1 expression in chronic hypoxia-induced pulmonary hypertension: role of NFATc3 and HuR

    PubMed Central

    de Frutos, Sergio; Nitta, Carlos H.; Caldwell, Elizabeth; Friedman, Jessica; González Bosc, Laura V.

    2009-01-01

    The nitric oxide/soluble guanylyl cyclase (sGC) signal transduction pathway plays an important role in smooth muscle relaxation and phenotypic regulation. However, the transcriptional regulation of sGC gene expression is largely unknown. It has been shown that sGC expression increases in pulmonary arteries from chronic hypoxia-induced pulmonary hypertensive animals. Since the transcription factor NFATc3 is required for the upregulation of the smooth muscle hypertrophic/differentiation marker ?-actin in pulmonary artery smooth muscle cells from chronically hypoxic mice, we hypothesized that NFATc3 is required for the regulation of sGC-?1 expression during chronic hypoxia. Exposure to chronic hypoxia for 2 days induced a decrease in sGC-?1 expression in mouse pulmonary arteries. This reduction was independent of NFATc3 but mediated by nuclear accumulation of the mRNA-stabilizing protein human antigen R (HuR). Consistent with our hypothesis, chronic hypoxia (21 days) upregulated pulmonary artery sGC-?1 expression, bringing it back to the level of the normoxic controls. This response was prevented in NFATc3 knockout and cyclosporin (calcineurin/NFATc inhibitor)-treated mice. Furthermore, we identified effective binding sites for NFATc in the mouse sGC-?1 promoter. Activation of NFATc3 increased sGC-?1 promoter activity in human embryonic derived kidney cells, rat aortic-derived smooth muscle cells, and human pulmonary artery smooth muscle cells. Our results suggest that NFATc3 and HuR are important regulators of sGC-?1 expression in pulmonary vascular smooth muscle cells during chronic hypoxia-induced pulmonary hypertension. PMID:19592461

  18. Effect of endurance training on seizure susceptibility, behavioral changes and neuronal damage after kainate-induced status epilepticus in spontaneously hypertensive rats.

    PubMed

    Tchekalarova, J; Shishmanova, M; Atanasova, D; Stefanova, M; Alova, L; Lazarov, N; Georgieva, K

    2015-11-01

    The therapeutic efficacy of regular physical exercises in an animal model of epilepsy and depression comorbidity has been confirmed previously. In the present study, we examined the effects of endurance training on susceptibility to kainate (KA)-induced status epilepticus (SE), behavioral changes and neuronal damage in spontaneously hypertensive rats (SHRs). Male SHRs were randomly divided into two groups. One group was exercised on a treadmill with submaximal loading for four weeks and the other group was sedentary. Immediately after the training period, SE was evoked in half of the sedentary and trained rats by KA, while the other half of the two groups received saline. Basal systolic (SP), diastolic (DP) and mean arterial pressure (MAP) of all rats were measured at the beginning and at the end of the training period. Anxiety, memory and depression-like behaviour were evaluated a month after SE. The release of 5-HT in the hippocampus was measured using a liquid scintillation method and neuronal damage was analyzed by hematoxylin and eosin staining. SP and MAP of exercised SHRs decreased in comparison with the initial values. The increased resistance of SHRs to KA-induced SE was accompanied by an elongated latent seizure-free period, improved object recognition memory and antidepressant effect after the training program. While the anticonvulsant and positive behavioral effects of endurance training were accompanied by an increase of 5-HT release in the hippocampus, it did not exert neuroprotective activity. Our results indicate that prior exercise is an effective means to attenuate KA-induced seizures and comorbid behavioral changes in a model of hypertension and epilepsy suggesting a potential influence of hippocampal 5-HT on a comorbid depression. However, this beneficial impact does not prevent the development of epilepsy and concomitant brain damage. PMID:26319691

  19. Comparison of. beta. -adrenergic receptors between different strains of rat with different susceptibility to hypertension: a survey of binding characteristics, responsiveness and corticosteroid induced modulation

    SciTech Connect

    Jazayeri, A.

    1987-01-01

    The objective of this research was two fold: the first objective was to measure ..beta..-adrenergic receptor characteristics (Bmax and Kd) and responsiveness (isoproterenol induced c-AMP production) between different strains of rat with different susceptibility to hypertension. The second objective of this research was to determine if ..beta..-adrenergic receptors of arterial smooth muscle cells (ASMC) can be modulated by corticosteroids. These studies were done under controlled conditions using ASMC grown in culture from the rat aorta. (/sup 3/H)-dihydroalprenolol (DHA) was used to measure ..beta..-adrenergic receptor binding characteristics (Kd and Bmax). Scatchard analysis of (/sup 3/H)-DHA binding revealed one class of binding sites with affinity in the range of 100 pM. (/sup 3/H)-DHA binding comparison between Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) revealed that the Bmax for SHR was significantly lower than WKY. However, isoproterenol stimulated c-AMP production by SHR, is significantly higher than WKY. Fischer 344 rats, showed similar Bmax, Kd, and responsiveness as WKY rats. Dahl-sensitive and Dahl-resistant rats had equal Bmax and Kd measured by (/sup 3/H)-DHA binding.

  20. Sex differences in primary hypertension

    PubMed Central

    2012-01-01

    Men have higher blood pressure than women through much of life regardless of race and ethnicity. This is a robust and highly conserved sex difference that it is also observed across species including dogs, rats, mice and chickens and it is found in induced, genetic and transgenic animal models of hypertension. Not only do the differences between the ovarian and testicular hormonal milieu contribute to this sexual dimorphism in blood pressure, the sex chromosomes also play a role in and of themselves. This review primarily focuses on epidemiological studies of blood pressure in men and women and experimental models of hypertension in both sexes. Gaps in current knowledge regarding what underlie male-female differences in blood pressure control are discussed. Elucidating the mechanisms underlying sex differences in hypertension may lead to the development of anti-hypertensives tailored to one's sex and ultimately to improved therapeutic strategies for treating this disease and preventing its devastating consequences. PMID:22417477

  1. Des-aspartate angiotensin I (DAA-I) reduces endothelial dysfunction in the aorta of the spontaneously hypertensive rat through inhibition of angiotensin II-induced oxidative stress.

    PubMed

    Loh, Wei Mee; Ling, Wei Chih; Murugan, Dharmani D; Lau, Yeh Siang; Achike, Francis I; Vanhoutte, Paul M; Mustafa, Mohd Rais

    2015-08-01

    Des-aspartate angiotensin I (DAA-I), an endogenous nonapeptide, counteracts several effects of angiotensin II on vascular tone. The aim of this study was to investigate the acute protective effect of DAA-I on endothelial function in the spontaneously hypertensive rat (SHR) as well as its effect on angiotensin II-induced contractions and oxidative stress. Aortic rings were incubated with DAA-I (0.1?M) for 30min prior to the assessment of angiotensin II-induced contractions (0.1nM-10?M) in WKY and SHR aortas. Total nitrate and nitrite levels were assessed using a colorimetric method and reactive oxygen species (ROS) were measured by dihydroethidium (DHE) fluorescence and lucigenin-enhanced chemiluminescence. The effect of DAA-I was also assessed against endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside, respectively. Angiotensin II-induced contractions were significantly reduced by DAA-I, losartan and tempol. Incubation with ODQ (soluble guanylyl cyclase inhibitor) and removal of the endothelium prevented the reduction of angiotensin II-induced contractions by DAA-I. Total nitrate and nitrite levels were increased in DAA-I, losartan and tempol treated-SHR tissues while ROS level was reduced by DAA-I and the latter inhibitors. In addition, DAA-I significantly improved the impaired acetylcholine-induced relaxation in SHR aortas whilst sodium nitroprusside-induced endothelium-independent relaxation remained unaffected. The present findings indicate that improvement of endothelial function by DAA-I in the SHR aorta is mediated through endothelium-dependent release of nitric oxide and inhibition of angiotensin II-induced oxidative stress. PMID:25869508

  2. Enhanced expression of epithelial sodium channels causes salt-induced hypertension in mice through inhibition of the ?2-isoform of Na+, K+-ATPase.

    PubMed

    Leenen, Frans H H; Hou, Xiaohong; Wang, Hong-Wei; Ahmad, Monir

    2015-05-01

    Knockout of the Nedd4-2 gene in mice results in overexpression of epithelial sodium channels (ENaC) on the plasma membrane in the kidney, choroid plexus and brain nuclei. These mice exhibit enhanced pressor responses to CSF [Na(+)] as well as dietary salt-induced hypertension which both can be blocked by central infusion of the ENaC blocker benzamil. Functional studies suggest that ENaC activation in the CNS results in release of endogenous ouabain (EO) and inhibition of the ?2-isoform of Na(+), K(+)-ATPase. To test this concept more specifically, we studied Nedd4-2(-/-) mice expressing the ouabain-resistant ?2R/R-isoform of Na(+), K(+)-ATPase. Intracerebroventricular (icv) infusion of Na(+)-rich aCSF (225 mmol/L Na(+) at 0.4 ?L/min) increased MAP by 10-15 mmHg in wild-type mice and by 25-30 mmHg in Nedd4-2(-/-) mice, but by only ~5 mmHg in ?2R/R and in ?2R/R/Nedd4-2(-/-) mice. Icv infusion of EO-binding Fab fragments also blocked the BP response in Nedd4-2(-/-) mice. In Nedd4-2(-/-) mice, 8% high-salt diet increased MAP by 25-30 mmHg, but in ?2R/R/Nedd4-2(-/-) mice, it increased by only 5-10 mmHg. In contrast, Nedd4-2(-/-) or ?2R/R did not affect the hypertension caused by sc infusion of Ang II. These findings substantiate the concept that enhanced ENaC activity causes salt-induced pressor responses mainly through EO inhibiting the ?2-isoform of Na(+), K(+)-ATPase in the brain. PMID:25991719

  3. Enhanced Ca(2+)-induced Ca(2+) release from intracellular stores contributes to catecholamine hypersecretion in adrenal chromaffin cells from spontaneously hypertensive rats.

    PubMed

    Segura-Chama, Pedro; López-Bistrain, Patricia; Pérez-Armendáriz, Elia Martha; Jiménez-Pérez, Nicolás; Millán-Aldaco, Diana; Hernández-Cruz, Arturo

    2015-11-01

    Adrenal chromaffin cells (CCs) from spontaneously hypertensive rats (SHRs) secrete more catecholamine (CA) upon stimulation than CCs from normotensive Wistar Kyoto rats (WKY). Unitary CA exocytosis events, both spontaneous and stimulated, were amperometrically recorded from cultured WKY and SHR CCs. Both strains display spontaneous amperometric spikes but SHR CCs produce more spikes and of higher mean amplitude. After a brief stimulation with high K(+) or caffeine which produces voltage-gated Ca(2+) influx or intracellular Ca(2+) release, respectively, more spikes and of greater mean amplitude and unitary charge were recorded in SHR CCs. Consequently, peak cumulative charge was ~2-fold higher in SHR CCs. Ryanodine (10 ?M), a specific blocker of the ryanodine receptors reduced depolarization-induced peak cumulative charge by ~10 % in WKY and ~77 % in SHR CCs, suggesting, a larger contribution of Ca(2+)-induced Ca(2+) release to CA exocytosis in SHR CCs. Accordingly, Ca(2+) imaging showed larger [Ca(2+)]i signals induced both by depolarization and caffeine in SHR CCs. Distribution amplitude histograms showed that small amperometric spikes (0-50 pA) are more frequent in WKY than in SHR CCs. Conversely, medium (50-190 pA) and large (190-290 pA) spikes are more numerous in SHR than in WKY CCs. This study reveals that the enhanced CA secretion in SHR CCs results from a combination of (1) larger depolarization-induced Ca(2+) transients, due to a greater Ca(2+)-induced intracellular Ca(2+) release, (2) more exocytosis events per time unit, and (3) a greater proportion of medium and large amperometric spikes probably due to a higher mean CA content per granule. Enhanced CA release by excessive amplification by Ca(2+) induced Ca(2+) release and larger granule catecholamine content contributes to the increased CA plasma levels and vasomotor tone in SHRs. PMID:25791627

  4. 11 -Hydroxysteroid Dehydrogenase Activity in Spontaneously Hypertensive and Dahl

    E-print Network

    Miksik, Ivan

    11 -Hydroxysteroid Dehydrogenase Activity in Spontaneously Hypertensive and Dahl Rats Irena Pohlova were therefore investigated in rats with spontaneous or salt-induced hypertension. The adult male rats of the following genotypes were used: spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY

  5. Hypertension (High Blood Pressure)

    MedlinePLUS

    ... Visitor Information RePORT NIH Fact Sheets Home > Hypertension (High Blood Pressure) Small Text Medium Text Large Text Hypertension (High Blood Pressure) YESTERDAY Hypertension is a silent killer because it ...

  6. Hormones and Hypertension

    MedlinePLUS

    Fact Sheet Hormones and Hypertension What is hypertension? Hypertension, or chronic (long-term) high blood pressure, is a main cause of ... tobacco, alcohol, and certain medications play a part. Hormones made in the kidneys and in blood vessels ...

  7. Types of Pulmonary Hypertension

    MedlinePLUS

    ... Hypertension The World Health Organization divides pulmonary hypertension (PH) into five groups. These groups are organized based ... lungs. Group 2 Pulmonary Hypertension Group 2 includes PH with left heart disease. Conditions that affect the ...

  8. Pulmonary Arterial Hypertension

    MedlinePLUS

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  9. Pulmonary Hypertension in Scleroderma

    MedlinePLUS

    PULMONARY HYPERTENSION IN SCLERODERMA PULMONARY HYPERTENSION Pulmonary hypertension (PH) is high blood pressure in the blood vessels ... with scleroderma are at increased risk for developing PH from several mechanisms. Frequently patients with scleroderma have ...

  10. Impromidine-induced changes in the permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats

    SciTech Connect

    Boertje, S.B.; Le Beau, D.; Ward, S. )

    1990-08-01

    Previous studies suggested histamine receptors mediate changes in the cerebrovascular permeability of rats. To test this, we investigated the effects of impromidine, a specific agonist at the histamine H2-receptor, on blood pressure and permeability of the blood-brain barrier (BBB). Impromidine produced dose-dependent hypotension in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Two higher doses of impromidine increased BBB permeability to 99mTc-sodium pertechnetate in WKY rats; however, two lower doses decreased permeability in SHR rats. All doses of impromidine increased cerebrovascular permeability to 131I-labeled serum albumin in both species. Doses of the drug were 100 times greater than those required to produce similar alterations using histamine.

  11. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    SciTech Connect

    Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan; Wen Fuqiang

    2010-05-15

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  12. Managing hypertension by polyphenols.

    PubMed

    Fernández-Arroyo, Salvador; Camps, Jordi; Menendez, Javier A; Joven, Jorge

    2015-06-01

    Some polyphenols, obtained from plants of broad use, induce a favorable endothelial response in hypertension and beneficial effects in the management of other metabolic cardiovascular risks. Previous studies in our laboratories using the calyces of Hibiscus sabdariffa as a source of polyphenols show that significant effects on hypertension are noticeable in humans only when provided in high amounts. Available data are suggestive in animal models and ex vivo experiments, but data in humans are difficult to acquire. Additionally, and despite the low bioavailability of polyphenols, intervention studies provide evidence for the protective effects of secondary plant metabolites. Assumptions on public health benefits are limited by the lack of scientific knowledge, robust data derived from large randomized clinical trials, and an accurate assessment of the bioactive components provided by common foodstuff. Because it is likely that clinical effects are the result of multiple interactions among different polyphenols rather than the isolated action of unique compounds, to provide polyphenol-rich botanical extracts as dietary supplements is a suggestive option. Unfortunately, the lack of patent perspectives for the pharmaceutical industries and the high cost of production and release for alimentary industries will hamper the performance of the necessary clinical trials. Here we briefly discuss whether and how such limitations may complicate the extensive use of plant-derived products in the management of hypertension and which steps are the necessary to deal with the predictable complexity in a possible clinical practice. PMID:25714729

  13. Early Training-Induced Reduction of Angiotensinogen in Autonomic Areas—The Main Effect of Exercise on Brain Renin-Angiotensin System in Hypertensive Rats

    PubMed Central

    Chaar, Laiali Jurdi; Alves, Tatiana Pereira; Batista Junior, Alvaro Martins; Michelini, Lisete Compagno

    2015-01-01

    Background Exercise training (T) blunts functional deficits and renin-angiotensin system (RAS) hyperactivity in hypertensive individuals. There is no information on T-induced temporal changes of brain RAS. We evaluate now the simultaneous effects of T on functional responses and time course changes in the expression/activity of brain RAS components in autonomic cardiovascular-controlling areas. Methods and Results Spontaneously hypertensive rats (SHR) and age-matched normotensive controls (WKY) were trained for 0, 1, 2, 4, 8 and 12 weeks. Sedentary (S) groups served as time-controls. After arterial pressure (AP) and heart rate (HR) recordings at rest, fresh and fixed brains were harvested for qPCR and immunofluorescence assays. SHR-S vs. WKY-S exhibited higher mean AP (MAP) and HR, increased pressure variability and sympathetic activity, elevated AT1 receptor (AT1) expression in nucleus tractus solitarii (NTS) and higher Mas receptor expression in the rostroventrolateral medulla (RVLM). In SHR, T promptly (T2 on) reduced sympathetic variability to heart/vessels and largely decreased angiotensinogen expression in the paraventricular hypothalamic nucleus (PVN) and NTS, with a late RVLM reduction (T4). AT1 expression was only reduced at T12 (PVN and NTS) with transient, not maintained Mas receptor changes in PVN and RVLM. These responses were accompanied by baseline MAP and HR reduction in the SHR-T (from T4 on). In the SHR group, PVN angiotensinogen expression correlated positively with sympathetic activity, resting MAP and HR. In WKY-T, a precocious (T2-T12) RVLM AT1 decrease preceded the appearance of resting bradycardia (from T8 on). Conclusions Early and maintained reduction of angiotensinogen content in autonomic areas of the SHR is the most prominent effect of training on brain RAS. Down-regulation of PVN RAS expression is an essential factor to drive cardiovascular benefits in SHR-T, while resting bradycardia in WKY-T is correlated to RVLM AT1 reduction. PMID:26372108

  14. Heat stress proteins in hypertension

    SciTech Connect

    Malo, D.; Tremblay, J.; Pang, S.C.; Schlager, G.; Hamet, P.

    1986-03-05

    It has been described that spontaneously hypertensive rats (SHR) are more sensitive to an acute environmental heat stress and that cultured cardiomyocytes from neonatal SHR are demonstrated to be more thermosensitive. In addition, chronically heat exposed spontaneously hypertensive mice leads to a decrease of blood pressure in these animals. Heat shock is known to induce the synthesis of a new set of proteins (HSP) in every cell tested. This ubiquitous response seems to be involved in the induction of a thermotolerant state. The synthesis of 70K HSP was observed in lymphocytes isolated from the spleen of chronically heated mice. They used lymphocytes, previously isolated on a ficoll gradient, to evaluate the HSP induction in normotensive (WKY) and hypertensive (SHR) rats. The heat shock was induced by exposing the lymphocytes at 46/sup 0/C during 5 min in a hot water bath. The cells were then labeled with (/sup 75/Se)-methionine, washed, homogenized and separated on 5-30% SDS-polyacrylamide gel. Preliminary results suggest an abnormal pattern of induction of 70K and 90K HSP in hypertension. Heat sensitivity, thermotolerance and expression of HSP may, thus, be related to hypertension.

  15. Essential Hypertension vs. Secondary Hypertension Among Children

    PubMed Central

    Banker, Ashish; Shete, Sanjay; Hashmi, Syed Sharukh; Tyson, John E.; Barratt, Michelle S.; Hecht, Jacqueline T.; Milewicz, Diane M.; Boerwinkle, Eric

    2015-01-01

    BACKGROUND The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. METHODS We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. RESULTS We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents”) from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3–17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08–19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P < 0.0001), and lower prevalence of preterm birth (20% vs. 46%; P < 0.001). There was a bimodal distribution of age of diagnosis in those with secondary hypertension. CONCLUSIONS The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth. PMID:24842390

  16. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    SciTech Connect

    Sung, Jin Young; Choi, Hyoung Chul

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  17. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

    PubMed

    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment. PMID:26132368

  18. Short-term dietary salt supplementation blunts telmisartan induced increases in plasma renin activity in hypertensive patients with type 2 diabetes mellitus.

    PubMed

    Chen, Angela X; Jerums, George; Baqar, Sara; Lambert, Elisabeth; Somarajah, Goji; Thomas, Georgina; O'Callaghan, Christopher; MacIsaac, Richard J; Ekinci, Elif I

    2015-09-01

    Current guidelines recommend low dietary salt intake (LDS) in patients with diabetes to reduce blood pressure (BP). However, low salt intake has been associated with higher mortality rates in people with diabetes. Our aim is to examine the effect of angiotensin II receptor blocker (ARB), telmisartan, with and without dietary sodium chloride (NaCl) supplementation, on BP [mean arterial pressure (MAP)], plasma renin activity (PRA), serum aldosterone level and estimated glomerular filtration rate (eGFR) in hypertensive patients with type 2 diabetes. In a randomized, double-blind, placebo-controlled study (RCT), 28 patients with type 2 diabetes, treated with telmisartan (40 mg daily), received 2 weeks of placebo or NaCl capsules (100 mmol/24 h). Following a 6-week washout, the protocol was repeated in reverse. Twenty-four-hour urinary sodium excretion (24hUNa), ambulatory BP (ABP) monitoring and blood tests were performed before and after each study phase. The telmisartan-associated increase in PRA was blunted by approximately 50% during salt supplementation compared with placebo; median PRA was 2.3 ?g/l/h with placebo compared with 1.7 ?g/l/h with salt (P<0.001). A trend towards blunting of ARB induced increases in serum aldosterone was also demonstrated. Salt supplementation significantly reduced the MAP lowering effects of telmisartan (P<0.05). The present study demonstrates that salt supplementation blunts the telmisartan induced increase in PRA in patients with type 2 diabetes. PMID:25849646

  19. Soluble Epoxide Hydrolase Is a Main Effector of Angiotensin IIInduced Hypertension

    E-print Network

    Hammock, Bruce D.

    Soluble Epoxide Hydrolase Is a Main Effector of Angiotensin II­Induced Hypertension Oliver JungEH contributes to angiotensin II­induced hypertension and tested the effects of a water-soluble sEH inhibitor, 12­induced hypertension (1 mg/kg per day). The effect of AUDA was accompanied by an increase in urinary salt and water

  20. Augmentation of ferulic acid-induced vasorelaxation with aging and its structure importance in thoracic aorta of spontaneously hypertensive rats.

    PubMed

    Fukuda, Toshihiko; Kuroda, Takahiro; Kono, Miki; Hyoguchi, Mai; Tanaka, Mitsuru; Matsui, Toshiro

    2015-10-01

    Aging deteriorates vascular functions such as vascular reactivity and stiffness. Thus far, various reports suggest that bioactive compounds can improve vascular functions. However, few age-related studies of natural bioactive compounds are available. The present study attempted to evaluate age-related vasorelaxation of bioactive cinnamic acids, caffeic acid, and ferulic acid using aged rat thoracic aorta. Vasorelaxation was evaluated in thoracic aorta from both 8, 18, and 40 weeks old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) respectively. The result indicated that caffeic acid possessed the vasorelaxation regardless of aging in WKY and SHR. Moreover, the vasorelaxation of ferulic acid enhanced with aging in SHR. The vasorelaxation behavior was acted in an endothelium-independent manner. To access structure importance of enhanced vasorelaxation, analogues of ferulic acid were tested. In 40 weeks old SHR, 3,4-dimethoxycinnamic acid and coniferyl alcohol exhibited equivalent vasorelaxation activity with ferulic acid, providing the structural importance of methoxy-modified 3-position on the phenyl ring and 2-propenoic moiety. These results firstly demonstrated that enhanced vasorelaxation of ferulic acid with aging and 3,4-dimethoxycinnamic acid and coniferyl alcohol, along with ferulic acid, might exhibit the therapeutic potential of vasoactive power with aging. PMID:26310777

  1. Microarray analysis after umbilical cord blood derived mesenchymal stem cells injection in monocrotaline-induced pulmonary artery hypertension rats

    PubMed Central

    Lee, Jae Chul; Kim, Kwan Chang; Yang, Yoon Sun; Oh, Wonil; Choi, Soo Jin

    2014-01-01

    Pulmonary arterial hypertension (PAH) is associated with structural alterations of lung vasculature. PAH is still a devastating disease needing an aggressive therapeutic approach. Despite the therapeutic potential of human umbilical cord mesenchymal stem cells (MSCs), the molecular parameters to define the stemness remain largely unknown. Using high-density oligonucleotide microarrays, the differential gene expression profiles between a fraction of mononuclear cells of human umbilical cord blood (UCB) and its MSC subpopulation were obtained. Of particular interest was a subset of 46 genes preferentially expressed at 7-fold or higher in the group treated with human UCB-MSCs. This subset contained numerous genes involved in the inflammatory response, immune response, lipid metabolism, cell adhesion, cell migration, cell differentiation, apoptosis, cell growth, transport, cell proliferation, transcription, and signal transduction. Our results provide a foundation for a more reproducible and reliable quality control using genotypic analysis for the definition of human UCB-MSCs. Therefore, our results will provide a basis for studies on molecular mechanisms controlling the core properties of human MSCs. PMID:25548719

  2. Cardiac metabolic alterations in hypertensive obese pigs.

    PubMed

    Zhang, Xin; Li, Zi-Lun; Eirin, Alfonso; Ebrahimi, Behzad; Pawar, Aditya S; Zhu, Xiang-Yang; Lerman, Amir; Lerman, Lilach O

    2015-08-01

    Obesity and hypertension are major risk factors for cardiovascular diseases, and their growing coexistence accounts for an increase in adverse cardiac events, but the mechanisms are yet to be determined. We hypothesized that obesity exacerbates mitochondrial dysregulation imposed by hypertension and augments left ventricular dysfunction. Obesity-prone Ossabaw pigs were randomized to lean (standard diet) and obese (high-fat diet), without (Lean-sham and Obese-sham) or with renovascular hypertension (Lean-hypertension and Obese-hypertension), induced after 12 weeks of diet (n=7 each). Cardiac function, myocardial perfusion and oxygenation, and microvascular remodeling were assessed 4 weeks later. Mitochondrial biogenesis signals and structural proteins, respiratory chain complex activities, and mitochondrial self-degradation were examined, as was fibrosis. Obesity alone exerted no apparent effect on mitochondrial dynamics, but aggravated in hypertensive hearts the reduction of mitochondrial proteins, deoxyribonucleic acid content, and respiratory chain complex IV subunits activity, and amplified mitochondrial self-degradation. Synergistic interaction of obesity with hypertension also exacerbated myocardial fibrosis and left ventricular diastolic dysfunction. Mitochondrial content, respiratory chain complex IV subunits activity, and mitophagy were correlated with myocardial fibrosis. These findings suggest that obesity aggravates in renovascular hypertension cardiac mitochondrial aberrations. Mitochondrial function may regulate the progression of cardiac injury and functional deterioration in hypertension concomitant with obesity. PMID:26077566

  3. Hypertensive Emergencies in Pregnancy.

    PubMed

    Olson-Chen, Courtney; Seligman, Neil S

    2016-01-01

    The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders. PMID:26600442

  4. Disease progression in iridocorneal angle tissues of BMP2-induced ocular hypertensive mice with optical coherence tomography

    PubMed Central

    Li, Guorong; Farsiu, Sina; Qiu, Jianming; Dixon, Angela; Song, Chunwei; McKinnon, Stuart J.; Yuan, Fan; Gonzalez, Pedro

    2014-01-01

    Purpose The goal of the present study was to test for the first time whether glaucomatous-like disease progression in a mouse can be assessed morphologically and functionally with spectral domain optical coherence tomography (SD-OCT). Methods We monitored progressive changes in conventional outflow tissues of living mice overexpressing human bone morphogenetic protein 2 (BMP2), a model for glaucoma. Intraocular pressure (IOP) and outflow tissue morphology/Young's modulus were followed in mice for 36 days with rebound tonometry and SD-OCT, respectively. Results were compared to standard histological methods. Outflow facility was calculated from flow measurements with direct cannulation of anterior chambers subjected to three sequential pressure steps. Results Overexpression of BMP2 significantly elevated IOP in a biphasic manner over time compared to mice that overexpressed green fluorescent protein in outflow cells and naïve controls. SD-OCT revealed changes in outflow tissues overexpressing BMP2 that corresponded with the timing of the IOP phases and decreased outflow facility. In the first phase, the angle was open, but the trabecular meshwork and the cornea were thickened. OCT detected increased trabecular meshwork stiffness after provocative IOP challenges of the BMP2 eyes, which corresponded to increased collagen deposition with transmission electron microscopy. In contrast, the angle was closed in the second phase. IOP elevation over 36 days due to BMP2 overexpression resulted in significant retinal ganglion cell and axon loss. Conclusions Although not a feasible open-angle glaucoma model, the BMP2 mice were useful for demonstrating the utility of SD-OCT in following disease progression and differentiating between two forms of ocular pathology over time that resulted in ocular hypertension. PMID:25558173

  5. Exaggerated hypertensive response to combretastatin A-4 phosphate in hypertensive rats: Effective pharmacological inhibition by diltiazem.

    PubMed

    Ke, Qingen; Samad, Mohammed A; Bae, Soochan; Chaplin, David J; Kang, Peter M

    2015-11-01

    Combretastatin A-4 phosphate (CA4P), a tubulin depolymerizing agent, shows promise in anti-cancer therapy and is associated with dose-dependent transient hypertension. The cardiac consequence of this hypertensive effect is unknown. This study was conducted to examine the cardiotoxic effect of CA4P on a rat model of hypertension. Hypertensive rats were created by feeding a 6% high salt (HS) diet to Dahl salt sensitive (DSS) rats for 2.5weeks. Cardiac toxicity was measured using serum troponin I levels 24h after CA4P administration. In rats fed HS diet, there was a significant increase in mean arterial blood pressure (MAP) from baseline, which was further increased by 80% following CA4P administration with peak systolic blood pressure (BP) of 247mmHg. Treatment with the calcium channel blockers, diltiazem and nicardipine, completely inhibited the hypertensive effects of CA4P. Nitroglycerin or enalapril, however, failed to completely block the hypertensive effects of CA4P. CA4P injection also significantly increased the cardiac troponin I level in hypertensive rats though pretreatment with diltiazem effectively blocked troponin I increase after CA4P administration. Based on these findings, an exaggerated hypertensive response to CA4P is associated with myocardial damage in hypertensive rats. Calcium channel blockers effectively blocked both CA4P induced hypertension and cardiac damage. PMID:25989107

  6. Restless legs syndrome and hypertension in Chinese pregnant women.

    PubMed

    Ma, Shengli; Shang, Xiaoping; Guo, Yu; Liu, Gangqiong; Yang, Jinjian; Xue, Rui

    2015-06-01

    Hypertension is a common complication of pregnancy, and studies show that pregnant women are more likely to suffer from restless legs syndrome (RLS). Pregnant women with hypertension and RLS often experience disrupted sleep patterns because of activation of the nervous system. The present study aimed to clarify the relationship between hypertension and RLS in pregnant women, and their impact on sleep. We enrolled 3,781 pregnant women who were admitted at our hospital for delivery between May 2011 and May 2014. The face-to-face questionnaire used to gather data included the International RLS Study Group criteria for diagnosis, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and hypertension diagnosis. Depending on the time of occurrence of hypertension, it was divided into two different types: pregnancy-induced hypertension and chronic hypertension in pregnancy. Out of 3,781 patients, 453 fulfilled the diagnostic criteria for RLS and 486 met the diagnostic criteria for hypertension. Among patients with RLS, prophylactic iron supplementation was less frequently taken during pregnancy. Pregnancy-induced hypertension, rather than chronic hypertension in pregnancy, was found to be more frequent in patients with RLS; pregnant women with RLS had higher PSQI and ESS scores than pregnant controls. In our study, RLS was frequent in pregnant women, especially in those without prophylactic iron supplementation. Patients with RLS described more serious sleep disruption and excessive daytime sleepiness (EDS). In addition, pregnancy-induced hypertension was more common in patients with RLS. PMID:25647293

  7. Hyperreninemic hypertension secondary to radiation nephritis in a child

    SciTech Connect

    Hulbert, W.C. Jr.; Ettinger, L.J.; Wood, B.P.; Anderson, V.M.; Putnam, T.C.; Rabinowitz, R.

    1985-08-01

    Radiation injury to the kidney, first reported almost eighty years ago, may vary from subclinical changes in renal blood flow or enzyme activity to clinically significant hypertension and/or renal failure. A child with radiation-induced hyperreninemic hypertension was cured by nephrectomy. The microscopic, subclinical, and clinical changes of irradiation injury are reviewed. The etiology of radiation-induced hypertension, methods of radioprotection, and early detection of radiation renal damage are discussed.

  8. Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model

    PubMed Central

    Zhen, Yen-Yi; Lu, Hung-I; Sung, Pei-Hsun; Chang, Li-Teh; Tsai, Tzu-Hsien; Sheu, Jiunn-Jye; Chen, Yung-Lung; Chua, Sarah; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan

    2014-01-01

    We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1?, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling. PMID:25587286

  9. Prolonged angina pectoris and persistent negative T waves in the precordial leads: response to atrial pacing and to methoxamine-induced hypertension

    SciTech Connect

    Figueras, J.; Cinca, J.; Gutierrez, L.; Segura, R.; Rius, J.

    1983-06-01

    In 18 consecutive patients without a history of myocardial infarction (MI), prolonged angina pectoris with persistent negative T waves in the precordial leads was associated with a high frequency of in-hospital spontaneous angina (14 of 18, 78%), usually accompanied by S-T segment elevation, and occasionally in-hospital MI (4 of 18, 22%). Angina and MI always involved the electrocardiographic leads with negative T waves. Coronary arteriography, performed in 16 patients, revealed greater than or equal to 90% proximal diameter reduction of the left anterior descending (LAD) coronary artery in 14 patients. No patient had severe narrowing of all 3 major coronary arteries, but the 3 who had 100% LAD occlusion lacked collateral circulation. The ejection fraction was greater than or equal to 50% in 13 patients. Atrial pacing performed in 11 patients at an average rate of 142 beats/min produced a 1.0 mm S-T segment change in only 5 patients (45%), 3 of whom had an associated lactate production. Arterial systemic hypertension induced by methoxamine in 14 patients caused reversal of negative T waves without significant S-T segment shifts or chest pain and failed to elicit lactate extraction abnormalities in each of the 5 patients in whom it was determined. Thus, prolonged angina with persistent negative T waves in the precordial leads is almost invariably associated with a critical and proximal LAD obstruction, severe narrowing of 1 or 2 coronary arteries, and poor or absent collateral vessels.

  10. Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model.

    PubMed

    Sun, Cheuk-Kwan; Zhen, Yen-Yi; Lu, Hung-I; Sung, Pei-Hsun; Chang, Li-Teh; Tsai, Tzu-Hsien; Sheu, Jiunn-Jye; Chen, Yung-Lung; Chua, Sarah; Chang, Hsueh-Wen; Chen, Yi-Ling; Lee, Fan-Yen; Yip, Hon-Kan

    2014-01-01

    We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1?, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling. PMID:25587286

  11. Refeeding hypertension in dietary obesity

    SciTech Connect

    Ernsberger, P.; Nelson, D.O. )

    1988-01-01

    A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state or mean arterial pressure under urethan anesthesia. In contrast, mild hypertension developed in intermittantly fasted obese animals. The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure accompanied the onset of supplemented fasting and was maintained thereafter. With refeeding, blood pressure rose precipitously, despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period. After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since (1) cardiac {beta}-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of ({sup 3}H)dihydroalpranolol; and (2) the decrease in heart rate as a result of {beta}-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension.

  12. Mechanisms and biomarkers of cardiovascular injury induced by phosphodiesterase inhibitor III SK&F 95654 in the spontaneously hypertensive rat.

    PubMed

    Zhang, Jun; Herman, Eugene H; Robertson, Donald G; Reily, Michael D; Knapton, Alan; Ratajczak, Helen V; Rifai, Nader; Honchel, Ronald; Blanchard, Kerry T; Stoll, Raymond E; Sistare, Frank D

    2006-01-01

    The cardiovascular injury of the type III selective PDE inhibitor SK&F 95654 was investigated in SHR. Twenty-four hours after a single sc injection of 100 or 200 mg/kg of the drug, rats exhibited cardiomyocyte necrosis and apoptosis, interstitial inflammation, hemorrhage and edema, as well as mesenteric arterial hemorrhage and necrosis, periarteritis, EC and VSMC apoptosis, EC activation, and MC activation and degranulation. Elevated serum levels of cTnT and decreased cTnT immunoperoxidase staining on cardiomyocytes were detected in the drug-treated rats. Serum levels of alpha2-macroglobulin and IL-6 were significantly elevated following drug treatment. NMR spectral patterns of urine samples are significantly different between the drug-treated and control rats. These results indicate that measurement of serum cTnT, acute phase proteins, and cytokines as well as metabonomic urine profiles may serve as potential biomarkers for drug-induced cardiovascular injury in rats. Increased expression of CD63 on MC (tissue biomarker of MC), of nitrotyrosine on MC and EC (an indirect indicator of NO in vivo), and of iNOS on MC and EC (source of NO) suggest that NO produced by activated and degranulated MC as well as activated EC play an important role in SK&F 95654-induced mesenteric vascular injury. PMID:16537294

  13. Hypertension in women

    PubMed Central

    Hage, Fadi G; Mansur, Sulaf J; Xing, Dongqi; Oparil, Suzanne

    2013-01-01

    Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestational hypertension, pre-eclampsia or eclampsia). Randomized controlled trials show that antihypertensive therapy provides similar reductions in major cardiovascular events in men and women. Therefore, gender should not influence decisions on selection of blood pressure lowering therapies, except for consideration of gender-specific side effects or contraindications for use in women who are or may become pregnant. This article reviews the prevalence, awareness, treatment, and control of hypertension in women, as well as recent guidelines for management of hypertension in women. PMID:25028640

  14. Living with Pulmonary Hypertension

    MedlinePLUS

    ... on Twitter. Living With Pulmonary Hypertension Pulmonary hypertension (PH) has no cure. However, you can work with ... your doctor advises. Call your doctor if your PH symptoms worsen or change. The earlier symptoms are ...

  15. What Causes Pulmonary Hypertension?

    MedlinePLUS

    ... on Twitter. What Causes Pulmonary Hypertension? Pulmonary hypertension (PH) begins with inflammation and changes in the cells ... also can affect the pulmonary arteries and cause PH. For example, the condition may develop if: The ...

  16. Cirrhosis and Portal Hypertension

    MedlinePLUS

    MENU Return to Web version Cirrhosis and Portal Hypertension Overview What is cirrhosis? In people who have ... lead to coma and death. What is portal hypertension? Normally, blood is carried to the liver by ...

  17. [Arterial hypertension in special situations: mild, systolic and in pregnancy].

    PubMed

    Luque Otero, M; Fernández Pinilla, C

    1990-01-01

    Mild hypertension is very common, 50% of hypertensives being with their diastolic BP between 90 and 104 mmHg. Many large studies, especially HDFP, had shown not only the deleterious cardiovascular effects of mild hypertension but also the benefits obtained with the therapy. The non-pharmacological approach should be the first step in the treatment of mild hypertension. Isolated systolic hypertension have a high prevalence in the elderly, increasing the cardiovascular morbidity and mortality. Sodium restriction and, if necessary, vasodilators increasing the arterial compliance seem to be the logical approach to treat isolated systolic hypertension. Finally, eclampsia is the most serious complication of pregnancy - induced hypertension. The treatment with bed rest and either betablockers or methyldopa is beneficial. If eclampsia occurs hydralazine, magnesium sulphate or nifedipine should be used. PMID:2186454

  18. NFKB1 promoter variation implicates shear-induced NOS3 gene expression and endothelial function in prehypertensives and stage I hypertensives

    PubMed Central

    Park, Joon-Young; Farrance, Iain K. G.; Fenty, Nicola M.; Hagberg, James M.; Roth, Stephen M.; Mosser, David M.; Wang, Min Qi; Jo, HanJoong; Okazaki, Toshihiko; Brant, Steven R.; Brown, Michael D.

    2008-01-01

    In endothelial cells, NF-?B is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether NF-? light-chain gene enhancer in B cells 1 (NFKB1) promoter polymorphism (?94NFKB1 I/D, where I is the insertion allele and D is the deletion allele) was associated with 1) NOS3 gene expression in endothelial cells under physiological levels of unidirectional laminar shear stress (LSS) and 2) endothelial function in prehypertensive and stage I hypertensive individuals before and after a 6-mo supervised endurance exercise intervention. Competitive EMSAs revealed that proteins present in the nuclei of endothelial cells preferentially bound to the I allele NFKB1 promoter compared with the D allele. Reporter gene assays showed that the I allele promoter had significantly higher activity than the D allele. In agreement with these observations, homozygous II genotype cells had higher p50 expression levels than homozygous DD genotype cells. Cells with the homozygous II genotype showed a greater increase in NOS3 protein expression than did homozygous DD genotype cells under LSS. Functional experiments on volunteers confirmed higher baseline reactive hyperemic forearm blood flow, and, furthermore, the subgroup analysis revealed that DD homozygotes were significantly less prevalent in the exercise responder group compared with II and ID genotypes. We conclude that the ?94NFKB1 I/D promoter variation contributes to the modulation of vascular function and adaptability to exercise-induced flow shear stress, most likely due to differences in NFKB1 gene transactivity. PMID:17644577

  19. Effect of aliskiren, telmisartan and torsemide on cardiac dysfunction in l-nitro arginine methyl ester (l-NAME) induced hypertension in rats.

    PubMed

    Sadek, Sawsan A; Rashed, Laila A; Bassam, Amira M; Said, Eman S

    2015-11-01

    Comparative study of cardio protective effect of aliskiren, telmisartan, and torsemide was carried out on l-nitro arginine methyl ester (l-NAME) induced hypertension in rats. The three drugs were given daily for 8 weeks simultaneously with l-NAME, with a control group for each drug and l-NAME. The degree of protection was assessed by measurement of systolic blood pressure and heart rate of animals every two weeks. At the end of the experimental period blood sampling was carried out for estimation of the level of NO2 (-)/NO3 (-). After which animals were sacrificed for heart dissection to detect collagen types I and III gene expression. Histopathological study was done to evaluate the extension of collagen deposits. The study revealed that the three drugs decreased blood pressure significantly compared to l-NAME. There was no significant difference between aliskiren and telmisartan in all measurements, but there was significant decrease in measurements of both aliskiren and telmisartan treated groups compared to torsemide starting from 4th week. There were insignificant changes in pulse rate values between the three l-NAME treated groups through the experiment. The three drugs significantly increased NO compared to l-NAME. Collagen I and III gene expression was significantly decreased by the three drugs but the highest percentage of inhibition was with telmisartan compared to l-NAME. Comparing the percentage inhibition of cardiac fibrosis, there was insignificant difference between telmisartan and torsemide treated groups while both were superior to aliskiren. In conclusion, further experimental studies are required to elucidate the potential cardioprotective mechanisms of aliskiren, telmisartan and torsemide, and assess their efficacy in treatment of heart failure. PMID:26644935

  20. Effect of aliskiren, telmisartan and torsemide on cardiac dysfunction in l-nitro arginine methyl ester (l-NAME) induced hypertension in rats

    PubMed Central

    Sadek, Sawsan A.; Rashed, Laila A.; Bassam, Amira M.; Said, Eman S.

    2014-01-01

    Comparative study of cardio protective effect of aliskiren, telmisartan, and torsemide was carried out on l-nitro arginine methyl ester (l-NAME) induced hypertension in rats. The three drugs were given daily for 8 weeks simultaneously with l-NAME, with a control group for each drug and l-NAME. The degree of protection was assessed by measurement of systolic blood pressure and heart rate of animals every two weeks. At the end of the experimental period blood sampling was carried out for estimation of the level of NO2?/NO3?. After which animals were sacrificed for heart dissection to detect collagen types I and III gene expression. Histopathological study was done to evaluate the extension of collagen deposits. The study revealed that the three drugs decreased blood pressure significantly compared to l-NAME. There was no significant difference between aliskiren and telmisartan in all measurements, but there was significant decrease in measurements of both aliskiren and telmisartan treated groups compared to torsemide starting from 4th week. There were insignificant changes in pulse rate values between the three l-NAME treated groups through the experiment. The three drugs significantly increased NO compared to l-NAME. Collagen I and III gene expression was significantly decreased by the three drugs but the highest percentage of inhibition was with telmisartan compared to l-NAME. Comparing the percentage inhibition of cardiac fibrosis, there was insignificant difference between telmisartan and torsemide treated groups while both were superior to aliskiren. In conclusion, further experimental studies are required to elucidate the potential cardioprotective mechanisms of aliskiren, telmisartan and torsemide, and assess their efficacy in treatment of heart failure. PMID:26644935

  1. Hypertension Research Division

    E-print Network

    Finley Jr., Russell L.

    Hypertension & Vascular Research Division Department of Internal Medicine Jeffrey L. Garvin, Ph.D. ­ Division Head #12;Prevalence of Hypertension in U.S. Men by Age and Ethnicity 18 ­ 29 30 ­ 39 40 ­ 49 50 Prevalence of High BP Adapted from Burt et al. Hypertension 1995;25:305. 25 50 75 #12;Introduction

  2. Vascular relaxation and cyclic guanosine monophosphate in hypertension

    SciTech Connect

    Otsuka, Y.; DiPiero, A.; Lockette, W.

    1986-03-01

    Isolated aortae from hypertensive rats have a decreased relaxation response to acetylcholine (Ach), A23187, and nitroprusside (SNP). Since cyclic guanosine monophosphate (cGMP) has been shown to increase in response to these vasodilators, the authors measured cGMP in response to these agents in isolated aortae from normotensive rats and DOCA, 1K1C, and coarctation induced hypertension. cGMP was measured by radioimmunoassay in vessels after exposure to phenylephrine followed by either Ach, A23187, or SNP. The aortae from the hypertensive rats had decreased basal levels of cGMP and attenuated increases in cGMP in response to Ach and A23187. Rises in cGMP in response to SNP were also attenuated in aortae from the hypertensive rats, even at concentrations which induced similar relaxation in normotensive and hypertensive blood vessels. The data suggest that changes in cGMP do not necessarily reflect changes in endothelium independent vascular relaxation in hypertension.

  3. Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury

    PubMed Central

    Hye Khan, Md. Abdul; Falck, John R.; Manthati, Vijaya L.; Campbell, William B.; Imig, John D.

    2014-01-01

    Epoxyeicosatrienoic acids (EETs) contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II)-induced hypertension. EET-B was administered in drinking water for 14 days (10 mg/kg/d) and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension. PMID:25295006

  4. [Neurogenic arterial hypertension in humans].

    PubMed

    Chamontin, B; Senard, J M; Amar, J; Doazan, J P; Guittard, J; Montastruc, J L; Salvador, M

    1989-07-01

    The purpose of this study was to investigate baroreflex activity in hypertensive patients with orthostatic hypotension (OH) due to sinoaortic baroreceptor denervation. The study concerned 3 patients (pts), 58-63 years, mean age 60.6 +/- 2 with both arterial hypertension (paroxysms recorded at 250/130 mmHg) and OH. They received radiation therapy to the entire cervical area for neoplasm, 9.6 +/- 2.8 years ago and had a carotid murmur without significant stenosis. Every pt had a severe and symptomatic OH: blood pressure (BP) and heart rate (HR) were respectively 163 +/- 17/105 +/- 7, 82 +/- 5 b/mn in lying position and 82 +/- 16/53 +/- 9 mmHg, 99 +/- 1 b/mm in standing position. The standing-induced increase in HR was lower (delta HR = + 17.3 b/mn) than expected; atropine (0.02 mg/kg) infusion and cold pressor test were ineffective; the massage of sinocarotid receptors induced a slight decrease in HR (delta HR = - 8 b/mn) and BP was not modified by Valsalva's maneuver. Infusion of norepinephrine (0.016 mg/mn) performed in one pt, increased BP without effect on HR. Platelet alpha 2-adrenoreceptors (alpha 2AR) evaluated by (3H) Yohimbine binding showed a significant increase in alpha 2AR number (Bmax), without any significant change in affinity (KD) when compared with normotensive and essential hypertensive pts: (table; see text) This study described an unusual etiology of a paroxysmal hypertension with orthostatic hypotension, demonstrated the impairment of baroreflex activity and suggested the potential interest of platelet alpha 2 adrenoceptors measurement to evaluate sympathetic tone in these patients. PMID:2510640

  5. [Theoretical considerations and comments on the physiopathology in renovascular hypertension].

    PubMed

    Burnei, Gh; Grigorean, V T; Gavriliu, St; Du?escu, S; Georgescu, I; Iacobini, M; Vlad, C; Stoian, A R; Burnei, A; Neac?u, C M

    2008-01-01

    The researches performed during the last four decades did not elucidate completely the pathogenic mechanism of the renovascular hypertension. The present knowledge considers that the origins of renovascular hypertension are the imbalance between the renal hypotensive system located in the medullar renal site (antihypertensive and hypotensive substances) and the renal hypertensive system (renin-angiotensin-aldosterone) located cortically. As an additional mechanism in producing hypertension is involved the disorder of hydro electrolytic metabolism, as a result of decreased excretory function, inducing an increase of plasmatic natrium level, of volemia and interstitial liquid. PMID:19274913

  6. HYPAZ: Hypertension Induced by Pazopanib

    ClinicalTrials.gov

    2015-07-18

    Renal Cell Carcinoma; Soft Tissue Sarcoma; Glioblastoma; Ovarian Cancer; Cervical Cancer; Breast Cancer; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Pancreatic Cancer; Melanoma; Gastrointestinal Cancer

  7. ?-Arrestin-1 protects against endoplasmic reticulum stress/p53-upregulated modulator of apoptosis-mediated apoptosis via repressing p-p65/inducible nitric oxide synthase in portal hypertensive gastropathy.

    PubMed

    Tan, Siwei; Li, Leijia; Chen, Tingting; Chen, Xiaoliang; Tao, Li; Lin, Xianyi; Tao, Jin; Huang, Xiaoli; Jiang, Jie; Liu, Huiling; Wu, Bin

    2015-10-01

    Portal hypertensive gastropathy (PHG) is a serious cause of bleeding in patients, and is associated with portal hypertension. ?-Arrestins (?-arrestin-1 and ?-arrestin-2) are well-established mediators of endocytosis of G-protein-coupled receptors (GPCRs), ubiquitination, and G-protein-independent signaling. The role of ?-arrestin-1 (?-arr1) in mucosal apoptosis in PHG remains unclear. The aim of this study was to investigate the involvement of ?-arr1 in PHG via its regulation of endoplasmic reticulum (ER) stress/p53-upregulated modulator of apoptosis (PUMA) apoptotic signaling. Gastric mucosal injury and apoptosis were studied in PHG patients and in PHG mouse models. The induction of ?-arr1 and the ER stress/PUMA signaling pathway were investigated, and the mechanisms of ?-arr1-regulated gastric mucosal apoptosis were analyzed in vivo and in vitro experiments. ?-arr1 and ER stress/PUMA signaling elements were markedly induced in the gastric mucosa of PHG patients and mouse models. Blockage of ER stress demonstrably attenuated the mucosal apoptosis of PHG, while targeted deletion of ?-arr1 significantly aggravated the injury and ER stress/PUMA-mediated apoptosis. ?-arr1 limited the activation of p65 to repress TNF-?-induced inducible nitric oxide synthase (iNOS) expression and NO release, which could regulate ER stress/PUMA-mediated mucosal apoptosis in PHG. In vivo and in vitro experiments further demonstrated that ?-arr1 protected against mucosal apoptosis by repressing TNF-?-induced iNOS expression via inhibiting the activation of p65. These results indicated that ?-arr1 regulated ER stress/PUMA-induced mucosal epithelial apoptosis through suppression of the TNF-?/p65/iNOS signaling pathway activation and that ?-arr1 is a potential therapeutic target for PHG. PMID:26119788

  8. [Hypertension in women].

    PubMed

    Tagle, Rodrigo; Tagle V, Rodrigo; Acevedo, Mónica; Valdés, Gloria

    2013-02-01

    The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages. PMID:23732498

  9. Pulmonary Hypertension in Sarcoidosis.

    PubMed

    Baughman, Robert P; Engel, Peter J; Nathan, Steven

    2015-12-01

    Pulmonary hypertension is a complication of sarcoidosis leading to dyspnea and associated with increased morbidity and mortality. Sarcoidosis-associated pulmonary hypertension (SAPH) can be due to several factors, including vascular involvement by the granulomatous inflammation, compression of the pulmonary arteries by adenopathy, fibrotic changes within the lung, and left ventricular diastolic dysfunction. Several case series have suggested that some patients with SAPH benefit from specific therapy for pulmonary hypertension. A randomized, placebo-controlled trial found 16 weeks' bosentan therapy to be associated with significant improvement in pulmonary artery pressure. Future studies may better define who would respond to treatment of pulmonary hypertension. PMID:26593143

  10. Pediatric endocrine hypertension.

    PubMed

    Bhavani, Nisha

    2011-10-01

    Endocrine causes of hypertension are rare in children and screening for endocrine hypertension in children should be carried out only after ruling out renal and renovascular causes. Excess levels and/or action of mineralocorticoids associated with low renin levels lead to childhood hypertension and this can be caused by various conditions which are discussed in detail in the article. Childhood pheochromocytomas are being increasingly diagnosed because of the improved application of genetic testing for familial syndromes associated with pheochromocytomas. Adolescents with polycystic ovarian syndrome (PCOS) can also have hypertension associated with their obese phenotype. PMID:22145140

  11. Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty

    E-print Network

    Hammock, Bruce D.

    Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid-induced hypertension model in wild-type (WT) but not KI mice. Furthermore, EET/dihydroxy-epoxyeicosatrienoic acid accounting for protection from hypertension afforded by the Mediterranean diet. thiol | cardiovascular

  12. [Portopulmonary hypertension with recurrent syncope: ?a case report and review of literature].

    PubMed

    Hou, Mengling; Liu, Ling; Peng, Daoquan; Li, Jiang

    2015-10-28

    A case of portopulmonary hypertension characterized by repeated syncope was retrospectively analyzed. Intrahepatic or extrahepatic factor-induced portal hypertension complicated with metabolic disorder of vasoactive substances, vascular pressure, inflammation, etc. may result in systolic and diastolic dysfunction of pulmonary arteries and systemic hyperdynamic circulation, the long-term effect of which can induce vascular remodeling and consequently, pulmonary hypertension. The pathogenic process is rather insidious. Pulmonary hypertension is clinically characterized by the raised average pulmonary artery pressure, normal pulmonary capillary wedge pressure and high pulmonary vascular resistance. Currently available therapeutic approaches include drug therapy targeting on pulmonary hypertension and liver transplantation. PMID:26541854

  13. Hypertension (High Blood Pressure)

    MedlinePLUS

    ... due to hypertension. The NIH is working with scientific and medical communities to update hypertension management guidelines (JNC-8), including integrating them with updated guidelines on management of cholesterol and obesity. For additional information please contact: Carl ... | RePORT Office of Science Policy Analysis | Office of Science Policy | Office of ...

  14. Chinese Hypertension Guidelines

    PubMed Central

    Wang, Ji-Guang

    2015-01-01

    According to the 4th National Nutrition and Health Survey in 2002, the prevalence of hypertension in China was 18.8%. Although there are no recent updated nationwide data, it is believed that the prevalence of hypertension has increased substantially in the past decade up to more than 200 million hypertensive patients in the populous country of China. To fight against the growing risk of hypertension, three Chinese hypertension guidelines were compiled in the past two decades, in 1999, 2005, and 2011. The current guidance document for the management of hypertension was named ‘2010 Chinese hypertension guideline’, but it was actually published in 2011. In this guideline, all five classes of antihypertensive drugs were recommended as possible initial and maintenance therapy. The goal of treatment was a systolic/diastolic blood pressure below 140/90 mm Hg in general, 130/80 mm Hg in various groups of high-risk patients, and 150/90 mm Hg in the elderly (?65 years). With the recent publication of several national and international hypertension guidelines, the Chinese guideline is now under discussion for updating.

  15. Noncirrhotic Portal Hypertension

    PubMed Central

    Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K

    2011-01-01

    Portal hypertension is characterized by an increase in portal pressure (> 10 mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic diseases. When portal hypertension occurs in the absence of liver cirrhosis, noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this disease is much better than that of cirrhosis. Noncirrhotic diseases are the common cause of portal hypertension in developing countries, especially in Asia. NCPH is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. In most cases, these disorders can be explained by endothelial cell lesions, intimal thickening, thrombotic obliterations, or scarring of the intrahepatic portal or hepatic venous circulation. Many different conditions can determine NCPH through the association of these various lesions in various degrees. Many clinical manifestations of NCPH result from the secondary effects of portal hypertension. Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae include hyperdynamic circulation, pulmonary complications, and other effects of portosystemic collateral circulation like portosystemic encephalopathy. At present, pharmacologic and endoscopic treatments are the treatments of choice for portal hypertension. The therapy of all disorders causing NCPH involves the reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart from prevention and treatment of complications of portal hypertension. PMID:25755321

  16. [Psychological factors in hypertension].

    PubMed

    Manuck, S; Morrison, R; Bellack, A

    1986-01-01

    We briefly overview behavioral factors of possible relevance to essential hypertension. We examine, in particular, dimensions of individual differences relating to: (a) problems of anger and assertion; and (b) cardiovascular responsivity to behavioral stressors. Hypertensive patients do show larger cardiovascular reactions to common laboratory stressors than normotensive, controls, and similar differences emerge in comparisons of normotensive individuals with and without a family history of hypertension. Concerning the purported dispositional attributes of hypertensives, we also propose re-examining psychodynamic notions regarding the suppression or denial of anger within a more objective, behavioral framework-specifically, as measurable deficits in assertive skill. Preliminary observations point to the presence of lower assertiveness in some hypertensive patients and increased hostility among others. These behavioral characteristics also appear to be associated with different patterns of cardiovascular reactivity, as recorded during interpersonal encounters that call for assertive responding. PMID:3512899

  17. Elevated Urinary T Helper 1 Chemokine Levels in Newly Diagnosed Hypertensive Obese Children

    PubMed Central

    Övünç Hac?hamdio?lu, Duygu; Zeybek, Cengiz; Gök, Faysal; Pekel, Aysel; Mu?abak, U?ur

    2015-01-01

    Objective: Increasing evidence suggests that T helper (Th) cells play a significant role in the pathogenesis of hypertension. The aim of this study was to evaluate the effect of obesity and anti-hypertensive treatment on urinary Th1 chemokines. Methods: The study groups consisted of three types of patients: hypertensive obese, healthy, and non-hypertensive obese. Pre-treatment and post-treatment samples of the hypertensive obese group and one sample from the other two groups were evaluated for urinary chemokine: regulated on activation, normal T cell expressed and secreted (RANTES), interferon-gamma-inducible protein 10 (IP10), and monokine induced by interferon-gamma (MIG). In the hypertensive obese group, urine microalbumin: creatinine ratio was examined before and after treatment. We recommended lifestyle changes to all patients. Captopril was started in those who could not be controlled with lifestyle changes and those who had stage 2 hypertension. Results: Twenty-four hypertensive obese (mean age 13.1), 27 healthy (mean age 11.2) and 22 non-hypertensive obese (mean age 11.5) children were investigated. The pre-treatment urine albumin: creatinine ratio was positively correlated with pre-treatment MIG levels (r=0.41, p<0.05). RANTES was significantly higher in the pre-treatment hypertensive and non-hypertensive obese group than in the controls. The urinary IP10 and MIG levels were higher in the pre-treatment hypertensive obese group than in the non-hypertensive obese. Comparison of the pre- and post-treatment values indicated significant decreases in RANTES, IP10, and MIG levels in the hypertensive obese group (p<0.05). Conclusion: Th1 cells could be activated in obese hypertensive children before the onset of clinical indicators of target organ damage. Urinary RANTES seemed to be affected by both hypertension and obesity, and urinary IP10 and MIG seemed to be affected predominantly by hypertension.

  18. [Holter EKG for the hypertensive heart disease].

    PubMed

    Galinier, M; Pathak, A; Fallouh, V; Baixas, C; Schmutz, L; Roncalli, J; Boveda, S; Fauvel, J M

    2002-12-01

    During chronic mechanical overload induced by hypertension, left ventricular hypertrophy predisposes to atrial and ventricular arrhythmias. Atrial arrhythmias, mainly atrial fibrillation, decrease cardiac output and increase the risk of embolism whereas ventricular arrhythmias remain the major cause of sudden death. In hypertensive patients, Holter EKG recordings frequently detect atrial or ventricular premature beats and more rarely atrial or ventricular tachycardia. In these patients, the presence of non-sustained ventricular tachycardia is considered as an independent predictor of mortality. Moreover, this non invasive method through the assessment of heart rate variability allows the study of the autonomic control of the heart, known to modulate occurrence of arrhythmias. PMID:12608125

  19. Neurohormonal Modulation of the Innate Immune System is Pro-inflammatory in the Pre-hypertensive Spontaneously Hypertensive Rat, a Genetic Model of Essential Hypertension

    PubMed Central

    Harwani, Sailesh C.; Chapleau, Mark W.; Legge, Kevin L.; Ballas, Zuhair K.; Abboud, Francois M.

    2012-01-01

    Rationale Inflammation and autonomic dysfunction contribute to the pathophysiology of hypertension. Cholinergic stimulation suppresses innate immune responses. Angiotensin II induces hypertension and is associated with pro-inflammatory immune responses. Objective Our goal was to define the innate immune response in a model of genetic hypertension and the influence of cholinergic stimulation and Ang II. Methods and Results Studies were conducted on 4–5 week old pre-hypertensive Spontaneously Hypertensive Rats (SHR) and age matched normotensive control, Wistar Kyoto (WKY) rats. Isolated splenocytes were pre-exposed to nicotine or Ang II prior to Toll-like Receptor (TLR) activation. Culture supernatants were tested for cytokines (TNF?, IL-10, and IL-6). TLR-mediated cytokine responses were most pronounced with TLR7/8 and TLR9 activation and similar between WKY and SHR. Nicotine and Ang II enhanced this TLR mediated IL-6 response in pre-hypertensive SHR splenocytes. In contrast, nicotine suppressed the TLR mediated IL-6 response in WKY, while Ang II had no effect. In vivo, nicotine enhanced plasma levels of TLR7/8 mediated IL-6 and IL-1? in pre-hypertensive SHR, but suppressed these responses in WKY. Flow cytometry revealed an increase in a CD161+ innate immune cell population, which was enhanced by nicotine in the pre-hypertensive SHR spleen, but not in WKY. Conclusions There is a pronounced anti-inflammatory nicotinic/cholinergic modulation of the innate immune system in WKY, which is reversed in pre-hypertensive SHR. The results support the novel concept that neurohormonal regulation of the innate immune system plays a role in the pathogenesis of genetic hypertension and provide putative molecular targets for treatment of hypertension. PMID:22904093

  20. Lung Disease and Hypertension

    PubMed Central

    Imaizumi, Yuki; Eguchi, Kazuo; Kario, Kazuomi

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) patients are at a high risk of developing cardiovascular diseases. Airflow limitation is a predictor of future risks of hypertension and cardiovascular events. COPD is now understood as a systemic inflammatory disease, with the focus on inflammation of the lungs. An association between inflammation and sympathetic overactivity has also been reported. In this article, we review the association between chronic lung disease and the risks of hypertension, cardiovascular morbidity, the underlying mechanisms, and the therapeutic approach to hypertension and cardiovascular diseases in patients with lung diseases.

  1. Management of Intracranial Hypertension

    PubMed Central

    Rangel-Castillo, Leonardo; Gopinath, Shankar; Robertson, Claudia S.

    2008-01-01

    Effective management of intracranial hypertension involves meticulous avoidance of factors that precipitate or aggravate increased intracranial pressure. When intracranial pressure becomes elevated, it is important to rule out new mass lesions that should be surgically evacuated. Medical management of increased intracranial pressure should include sedation, drainage of cerebrospinal fluid, and osmotherapy with either mannitol or hypertonic saline. For intracranial hypertension refractory to initial medical management, barbiturate coma, hypothermia, or decompressive craniectomy should be considered. Steroids are not indicated and may be harmful in the treatment of intracranial hypertension resulting from traumatic brain injury. PMID:18514825

  2. Perioperative hypertension management

    PubMed Central

    Varon, Joseph; Marik, Paul E

    2008-01-01

    Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension. PMID:18827911

  3. Hypertension in pregnancy.

    PubMed

    Solomon, Caren G; Seely, Ellen W

    2011-12-01

    Hypertension is a common complication of pregnancy. Preeclampsia, in particular, is associated with substantial risk to both the mother and the fetus. Several risk factors have been recognized to predict risk for preeclampsia. However, at present no biomarkers have sufficient discriminatory ability to be useful in clinical practice, and no effective preventive strategies have yet been identified. Commonly used medications for the treatment of hypertension in pregnancy include methyldopa and labetalol. Blood pressure thresholds for initiating antihypertensive therapy are higher than outside of pregnancy. Women with prior preeclampsia are at increased risk of hypertension, cardiovascular disease, and renal disease. PMID:22108284

  4. Aortic wall proteomic analysis in spontaneously hypertensive rats with a blood pressure decrease induced by 6-week load-free swimming

    PubMed Central

    FENG, HONG; LI, HAIYING; ZHANG, DERONG; ZHAO, YUNGANG; JIANG, NING; ZHAO, XIAOLING; ZHANG, YU; TAN, JUNZHEN; FANG, WEN; ZHANG, YONG; LIU, WEI

    2015-01-01

    Decreased arterial compliance is one of the earliest detectable manifestations of adverse structural and functional changes within the vessel wall in hypertension. The proteomic approach is a powerful technique to analyze a complex mixture of proteins in various settings. Physical activity level was negatively associated with blood pressure. Sixteen 4-week-old male spontaneously hypertensive rats (SHR) and 16 Wistar-Kyoto (WKY) rats were randomly divided into four groups: i) SHR exercise group, ii) SHR rest group, iii) WKY exercise group and iv) WKY rest group. In the SHR and WKY exercise groups, rats were treated with a 6-week load-free swimming protocol (1 h/day, 5 days/week). The blood pressure of the rats was tested by the CODATM2 single non-invasive blood pressure measurement appliance. After the 6-week swimming protocol, the total aorta excluding abdominal aorta was extracted. The proteins were separated by two-dimensional gel electrophoresis and identified via LC-mass spectrometry (MS)/MS. After 6-week load-free swimming, blood pressure decreased in the SHRs. Compared with sedentary SHRs, 11 spots on the 2D-gel showed a significant difference in exercised SHRs. Nine of these were chosen for further identification. There were 5 upregulated proteins (long-chain specific acyl-CoA dehydrogenase, heat shock protein ?-1, isocitrate dehydrogenase subunit ?, actin, ? cardiac muscle 1 preprotein and calmodulin isoform 2) and 4 downregulated proteins (adipocyte-type fatty acid-binding protein, tubulin ?-2C chain, 78 kDa glucose-regulated protein precursor and mimecan). Proteomics is an effective method to identify the target proteins of exercise intervention for hypertension. PMID:26405545

  5. Orexin, cardio-respiratory function, and hypertension

    PubMed Central

    Li, Aihua; Nattie, Eugene

    2014-01-01

    In this review we focus on the role of orexin in cardio-respiratory functions and its potential link to hypertension. (1) Orexin, cardiovascular function, and hypertension. In normal rats, central administration of orexin can induce significant increases in arterial blood pressure (ABP) and sympathetic nerve activity (SNA), which can be blocked by orexin receptor antagonists. In spontaneously hypertensive rats (SHRs), antagonizing orexin receptors can significantly lower blood pressure under anesthetized or conscious conditions. (2) Orexin, respiratory function, and central chemoreception. The prepro-orexin knockout mouse has a significantly attenuated ventilatory CO2 chemoreflex, and in normal rats, central application of orexin stimulates breathing while blocking orexin receptors decreases the ventilatory CO2 chemoreflex. Interestingly, SHRs have a significantly increased ventilatory CO2 chemoreflex relative to normotensive WKY rats and blocking both orexin receptors can normalize this exaggerated response. (3) Orexin, central chemoreception, and hypertension. SHRs have higher ABP and SNA along with an enhanced ventilatory CO2 chemoreflex. Treating SHRs by blocking both orexin receptors with oral administration of an antagonist, almorexant (Almxt), can normalize the CO2 chemoreflex and significantly lower ABP and SNA. We interpret these results to suggest that the orexin system participates in the pathogenesis and maintenance of high blood pressure in SHRs, and the central chemoreflex may be a causal link to the increased SNA and ABP in SHRs. Modulation of the orexin system could be a potential target in treating some forms of hypertension. PMID:24574958

  6. Hypertensive heart disease

    MedlinePLUS

    ... failure: pathophysiology and diagnosis. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  7. High Blood Pressure (Hypertension)

    MedlinePLUS

    ... For Consumers Consumer Information by Audience For Women High Blood Pressure (Hypertension) Share Tweet Linkedin Pin it More sharing options ... En Español Who is at risk? How is high blood pressure treated? Understanding your blood pressure: What do the ...

  8. Pathophysiology of Portal Hypertension

    PubMed Central

    Iwakiri, Yasuko

    2014-01-01

    Portal hypertension is a major complication of liver disease, which results from a variety of pathological conditions that increase the resistance to the portal blood flow into the liver. The primary cause of portal hypertension in cirrhosis is an increase in intrahepatic vascular resistance due to massive structural changes associated with fibrosis and increased vascular tone in the hepatic microcirculation. As portal hypertension develops, the formation of collateral vessels and arterial vasodilation progress, which results in increased blood flow to the portal circulation. Eventually the hyperdynamic circulatory syndrome develops, leading to esophageal varices or ascites. This review article will summarize the factors that increase 1) intrahepatic vascular resistance and 2) the blood flow in the splanchnic and systemic circulations in liver cirrhosis. Finally, the future directions of basic/clinical research in portal hypertension will be discussed. PMID:24679494

  9. Neural regulation of hypoxia-inducible factors and redox state drives the pathogenesis of hypertension in a rodent model of sleep apnea.

    PubMed

    Semenza, Gregg L; Prabhakar, Nanduri R

    2015-11-15

    Obstructive sleep apnea (OSA) is one of the most common causes of hypertension in western societies. OSA causes chronic intermittent hypoxia (CIH) in specialized O2-sensing glomus cells of the carotid body. CIH generates increased reactive oxygen species (ROS) that trigger a feedforward mechanism in which increased intracellular calcium levels ([Ca(2+)]i) trigger increased HIF-1? synthesis and increased HIF-2? degradation. As a result, the normal homeostatic balance between HIF-1?-dependent prooxidant and HIF-2?-dependent antioxidant enzymes is disrupted, leading to further increases in ROS. Carotid body sensory nerves project to the nucleus tractus solitarii, from which the information is relayed via interneurons to the rostral ventrolateral medulla in the brain stem, which sends sympathetic neurons to the adrenal medulla to stimulate the release of epinephrine and norepinephrine, catecholamines that increase blood pressure. At each synapse, neurotransmitters trigger increased [Ca(2+)]i, HIF-1?:HIF-2?, and Nox2:Sod2 activity that generates increased ROS levels. These responses are not observed in other regions of the brain stem that do not receive input from the carotid body or signal to the sympathetic nervous system. Thus sympathetic nervous system homeostasis is dependent on a balance between HIF-1? and HIF-2?, disruption of which results in hypertension in OSA patients. PMID:25953833

  10. Resistant Hypertension and Chronotherapy

    PubMed Central

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-01-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing’s syndrome, thyroid diseases, aortic coarctation. For diagnosing patient’s history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of “non-dipper” hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  11. Resistant hypertension and chronotherapy.

    PubMed

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-04-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing's syndrome, thyroid diseases, aortic coarctation. For diagnosing patient's history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of "non-dipper" hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  12. Dissociation of changes in the permeability of the blood-brain barrier from catecholamine-induced changes in blood pressure of normotensive and spontaneously hypertensive rats

    SciTech Connect

    Sankar, R.; Domer, F.R.; Taylor, B.

    1982-09-01

    Researchers have studied the effects of the pressor catecholamine, dopamine, and the depressor catecholamine, isoproterenol, on the systemic blood pressure and the permeability of the blood-brain barrier (BBB) to albumin in normotensive (WKY) and spontaneously hypertensive (SHR) rats. The rats were anesthetized with pentobarbital. The permeability of the BBB to protein was measured by the extravasation of radioiodinated serum albumin (RISA). The permeability was decreased by both catecholamines despite the dose-dependent, yet opposite, changes in blood pressure in the WKY rats. The blood pressure response to both of the catecholamines was enhanced in the SHR rats. Isoproterenol caused a decrease in the permeability of the BBB in the SHR but dopamine did not. Results with both WKY and SHR rats are suggestive of an adrenergically-mediated decrease in movement across the BBB of compounds of large molecular weight, regardless of changes in blood pressure.

  13. Knowledge and awareness of hypertension among patients with systemic hypertension.

    PubMed Central

    Familoni, B. Oluranti; Ogun, S. Abayomi; Aina, A. Olutoyin

    2004-01-01

    BACKGROUND: In Nigeria, systemic hypertension is the commonest noncommunicable disease, and public awareness about hypertension and its determinants is poor. This study aims to assess the knowledge and level of awareness of the disease among hypertensive patients attending the medical outpatient clinic of Olabisi Onabanjo University Teaching Hospital (OOUTH). METHODOLOGY: Hypertensive patients who attended the medical outpatient clinic during the one-year study period and gave their consent were recruited into the study. Response to a questionnaire on various aspects of hypertension was analyzed using the STATA for Windows software. RESULTS: There were 254 hypertensive patients, of which 111 were males and 143 were females, giving a male: female ratio of 1:1.3. The mean age (SD) of the patients was 51 years +/- 12.2; 52.4% of the participants were aware that hypertension was the commonest noncommunicable disease in Nigeria. About one in 10 patients (11.4%) was aware that "nil symptom" is the commonest symptom of hypertension, while 37% were not aware that hypertension could cause renal failure. Only about one-third (35.4%) of the patients knew that hypertension should ideally be treated for life, while 58.3% believed that antihypertensive drugs should be used only when there are symptoms. The remaining 6.3% believed that the treatment of hypertension should be for periods ranging from two weeks to five years but not for life. CONCLUSION: This study has demonstrated inadequate knowledge of hypertension in patients with hypertension in our study population. Conscious efforts should be made and time set aside to health educate hypertensive patients. Organization of "hypertensive club or society" could be encouraged. These will reduce dissemination of false or inaccurate information by hypertensive patients to the public and its attendant dangers. PMID:15160976

  14. How Is Pulmonary Hypertension Treated?

    MedlinePLUS

    ... Twitter. How Is Pulmonary Hypertension Treated? Pulmonary hypertension (PH) has no cure. However, treatment may help relieve symptoms and slow the progress of the disease. PH is treated with medicines, procedures, and other therapies. ...

  15. How Is Pulmonary Hypertension Diagnosed?

    MedlinePLUS

    ... Hypertension Diagnosed? Your doctor will diagnose pulmonary hypertension (PH) based on your medical and family histories, a ... exam, and the results from tests and procedures. PH can develop slowly. In fact, you may have ...

  16. Methamphetamine Use and Pulmonary Hypertension

    MedlinePLUS

    Methamphetamine Use Pulmonary & PH Hypertension Did you know that if you have used methamphetamines you are at risk for Pulmonary Hypertension? www. ... are made every year. PH in Association with Methamphetamine Use My doctor recently told me that I ...

  17. A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice

    PubMed Central

    Choi, Ko-Eun; Hall, Casey L.; Sun, Jin-Mei; Wei, Ling; Mohamad, Osama; Dix, Thomas A.; Yu, Shan P.

    2012-01-01

    Compelling evidence from preclinical and clinical studies has shown that mild to moderate hypothermia is neuroprotective against ischemic stroke. Clinical applications of hypothermia therapy, however, have been hindered by current methods of physical cooling, which is generally inefficient and impractical in clinical situations. In this report, we demonstrate the potential of pharmacologically induced hypothermia (PIH) by the novel neurotensin receptor 1 (NTR1) agonist ABS-201 in a focal ischemic model of adult mice. ABS-201 (1.5–2.5 mg/kg, i.p.) reduces body and brain temperature by 2–5°C in 15–30 min in a dose-dependent manner without causing shivering or altering physiological parameters. Infarct volumes at 24 h after stroke are reduced by ?30–40% when PIH therapy is initiated either immediately after stroke induction or after 30–60 min delay. ABS-201 treatment increases bcl-2 expression, decreases caspase-3 activation, and TUNEL-positive cells in the peri-infarct region, and suppresses autophagic cell death compared to stroke controls. The PIH therapy using ABS-201 improves recovery of sensorimotor function as tested 21 d after stroke. These results suggest that PIH induced by neurotensin analogs represented by ABS-201 are promising candidates for treatment of ischemic stroke and possibly for other ischemic or traumatic injuries. Choi, K.-E., Hall, C. L., Sun, J.-M., Wei, L., Mohamad, O., Dix, T. A., Yu, S. P. A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice. PMID:22459147

  18. [Treatment of hypertension crises].

    PubMed

    Tanabe, Akiyo

    2015-11-01

    A hypertensive emergency is medical condition with severe hypertension involves acute and rapidly progressed target cardiovascular organ damage. This situation requires immediate blood pressure reduction to prevent lethal target-organ damage. A patient must be treated under intensive-care monitoring and with intravenous antihypertensive medicines. To avoid organ ischemia which is caused by rapid reduction in blood pressure, the recommended aims are reduction of mean arterial pressure by no more than 25% during the first one hour, followed by 160/100-110 mmHg within the next 2-6 hours. While a hypertensive urgency which does not accompany any evidence of target-organ damages can be treated with oral antihypertensives agents. PMID:26619669

  19. [Therapy of hypertension--2015].

    PubMed

    Kintscher, Ulrich; Mahfoud, Felix

    2015-05-01

    With an prevalence of 32%, arterial hypertension remains on of the most common diseases among adults in Germany. The ESH/ESC-guidelines from 2013 and the corresponding pocket guidelines of the DHL(®)/DGK from 2014 contain multiple modifications in diagnosis and therapy that are discussed in the present review. Target blood pressure recommendations have been simplified to <140/90 mmHg for almost all hypertensive patients. Exceptions include: diabetic patients, elderly, and patients with chronic kidney disease and proteinuria. The recommendations for pharmacological antihypertensive therapy remained mainly unchanged. Critical evaluation of renal denervation in therapy resistant hypertension requires additional randomized controlled trials in Germany to finally assess the clinical relevance of this intervention. Currently, renal denervation does not provide an alternative strategy for an established pharmacological or non-pharmacological approach. PMID:26080725

  20. Chronic thromboembolic pulmonary hypertension.

    PubMed

    O'Connell, Caroline; Montani, David; Savale, Laurent; Sitbon, Olivier; Parent, Florence; Seferian, Andrei; Bulifon, Sophie; Fadel, Elie; Mercier, Olaf; Mussot, Sacha; Fabre, Dominique; Dartevelle, Philippe; Humbert, Marc; Simonneau, Gérald; Jaïs, Xavier

    2015-12-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension (PH) characterized by the persistence of thromboembolic obstructing the pulmonary arteries as an organized tissue and the presence of a variable small vessel arteriopathy. The consequence is an increase in pulmonary vascular resistance resulting in progressive right heart failure. CTEPH is classified as group IV pulmonary hypertension according to the WHO classification of pulmonary hypertension. CTEPH is defined as precapillary pulmonary hypertension (mean pulmonary artery pressure?25mmHg with a pulmonary capillary wedge pressure?15mmHg) associated with mismatched perfusion defects on ventilation-perfusion lung scan and signs of chronic thromboembolic disease on computed tomography pulmonary angiogram and/or conventional pulmonary angiography, in a patient who received at least 3 months of therapeutic anticoagulation. CTEPH as a direct consequence of symptomatic pulmonary embolism (PE) is rare, and a significant number of CTEPH cases develop in the absence of history of PE. Thus, CTEPH should be considered in any patient with unexplained PH. Splenectomy, chronic inflammatory conditions such as inflammatory bowel disease, indwelling catheters and cardiac pacemakers have been identified as associated conditions increasing the risk of CTEPH. Ventilation-perfusion scan (V/Q) is the best test available for establishing the thromboembolic nature of PH. When CTEPH is suspected, patients should be referred to expert centres where pulmonary angiography, right heart catheterization and high-resolution CT scan will be performed to confirm the diagnosis and to assess the operability. Pulmonary endarterectomy (PEA) remains the gold standard treatment for CTEPH when organized thrombi involve the main, lobar or segmental arteries. This operation should only be performed by experienced surgeons in specialized centres. For inoperable patients, current ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension recommend the use of riociguat and say that off-label use of drugs approved for PAH and pulmonary angioplasty may be considered in expert centres. PMID:26585271

  1. Different relations between schedule-induced polydipsia and impulsive behaviour in the Spontaneously Hypertensive Rat and in high impulsive Wistar rats: questioning the role of impulsivity in adjunctive behaviour.

    PubMed

    Ibias, Javier; Pellón, Ricardo

    2014-09-01

    Rats belonging to three different strains (15 Wistar, 8 Spontaneously Hypertensive - SHR- and 8 Wistar Kyoto - WKY-) were used to evaluate the possible relationship between different levels of impulsivity and development of schedule-induced polydipsia (SIP). We first measured the rats' levels of impulsivity by means of delay-discounting and indifference-point procedures. Secondly, development of SIP was studied under a series of fixed time 15, 30, 60 and 120s food schedules, which were counterbalanced by means of a Latin-square design. Finally, we re-assessed the rats' levels of impulsivity by replicating the delay-discounting test. The findings showed that, starting from equivalent levels of impulsivity, development of SIP differed among the groups of rats. In comparison with the rest of the animals, the SHRs were observed to attain elevated drinking rates under SIP. On the other hand, the Wistar rats which had initial high impulsivity levels similar to those of the SHRs, displayed the lowest rates of induced drinking. Moreover, low levels of impulsivity in Wistar rats prior to SIP acquisition were reflected into high drinking rates. Relation of SIP and impulsivity is questioned by present results, which gives ground to the understanding of the behavioural mechanisms involved in adjunctive behaviour and its usefulness as an animal model of excessive behaviour. PMID:24931797

  2. 1,25 (OH) sub 2 vitamin D sub 3 -induced sup 45 Ca uptake in vascular myocytes cultured from spontaneously hypertensive and normotensive rats

    SciTech Connect

    Xue, Hong; McCarron, D.A.; Bukoski, R.D. )

    1991-01-01

    The effect of 1,25 (OH){sub 2} vitamin D{sub 3} on basal {sup 45}Ca uptake was examined in vasvular smooth muscle cells cultured from mesenteric arteries of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats. Basal uptake of {sup 45}Ca was significantly greater in myocytes of WKY than SHR at 5, 10, 30 and 60 min incubation with the isotope. Incubation with 1 ng/ml 1,25 (OH){sub 2} vitamin D{sub 3} for 48 hr increased basal {sup 45}Ca uptake between 1-10 min in SHR and between 5-10 min in WKY. The dose-response relationship indicated that cells from both strains are equally sensitive to the calciotropic effects of 1,25 (OH){sub 2} vitamin D{sub 3} with half-maximal stimulation occurring at approximately 0.3-0.4 ng/ml. In cells of both strains maximal stimulation of {sup 45}Ca uptake was achieved only after a 12-24 hr period of incubation with hormone and pretreatment with cycloheximide inhibited 1,24 (OH){sub 2} vitamin D{sub 3}-enhanced {sup 45}Ca uptake. Although {sup 45}Ca binding by extracellular matrix material was significantly greater in WKY than SHR, 1,25 (OH){sub 2} vitamin D{sub 3} had no effect on the amount of matrix {sup 45}Ca binding in either strain.

  3. Temporal differences in the development of organ dysfunction based on two different approaches to induce experimental intra-abdominal hypertension in swine

    PubMed Central

    2012-01-01

    Background Intra-abdominal hypertension [IAH] occurs frequently among critically ill patients and is associated with increased mortality and organ failure. Two porcine models of IAH that cause abdominal compartment syndrome [ACS] with organ dysfunction were created. We investigated whether the two methods used to create IAH - CO2 pneumoperitoneum or adding volume to the intra-abdominal space - exerted different impacts on the temporal development of organ dysfunction. Methods Twenty-four 40-kg female pigs were allocated to four groups: 25 mmHg IAH with CO2 pneumoperitoneum (n = 8), >20 mmHg IAH caused by addition of volume (n = 8), and two corresponding sham groups (each n = 4). The two sham groups were later pooled into one control group (n = 8). The animals were monitored for 12 h. Repeated serial measurements were taken of group differences over time and analyzed using analysis of variance. Results Thirty-eight percent of the animals (n = 3) in each intervention group died near the end of the 12-h experiment. Both intervention groups experienced kidney impairment: increased creatinine concentration (P <0.0001), anuria (P = 0.0005), hyperkalemia (P <0.0001), decreased abdominal perfusion pressure, and decreased dynamic lung compliance. CO2 pneumoperitoneum animals developed hypercapnia (P <0.0001) and acidosis (P <0.0001). Conclusions Both methods caused ACS and organ dysfunction within 12 h. Hypercapnia and acidosis developed in the CO2 pneumoperitoneum group. PMID:24266989

  4. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants

    PubMed Central

    Baradaran, Azar; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented. PMID:25097610

  5. Hypertension management in patients with renal cell cancer treated with anti-angiogenic agents

    PubMed Central

    Larochelle, P.; Kollmannsberger, C.; Feldman, R.D.; Schiffrin, E.L.; Poirier, L.; Patenaude, F.; Ruether, D.; Myers, M.; Bjarnason, G.

    2012-01-01

    Inhibitors of the vascular endothelial growth factor (vegf-is) signalling pathway have fundamentally changed the treatment of metastatic renal cell carcinoma (mrcc). Hypertension is one of the most common side effects of vegf-is and has been reported with almost every vegf-i used for treatment to date. The exact mechanism of vegf-i–induced hypertension appears complex and multifactorial, and it remains to be fully explained. No randomized clinical trials are available to guide the management of hypertension during vegf-i treatment in mrcc patients. The guiding principles suggested here summarize the consensus of opinions on the diagnosis and management of vegf-i–induced hypertension during treatment of mrcc obtained from an expert working group composed of 4 Canadian medical oncologists and 5 Canadian hypertension specialists. The Canadian Hypertension Education Program guidelines, available literature, and expert opinion were used to develop the guiding principles. PMID:22876146

  6. Molecular Mechanism of Aggravation of Hypertensive Organ Damages by Short-Term Blood Pressure Variability

    PubMed Central

    Kai, Hisashi; Kudo, Hiroshi; Takayama, Narimasa; Yasuoka, Suguru; Aoki, Yuji; Imaizumi, Tsutomu

    2015-01-01

    There is increasing evidence that not only the elevation of systolic and diastolic blood pressure (BP) but also the increase in BP variability (or fluctuation) are associated with hypertensive organ damages and the morbidity and mortality of cerebrovascular and cardiovascular events. However, the molecular mechanism whereby the increase in BP variability aggravates hypertensive organ damages remains unknown. Thus, we created a rat chronic model of a combination of hypertension and large BP variability by performing bilateral sino-aortic denervation in spontaneously hypertensive rat. A series of our studies using this model revealed that large BP variability induces chronic myocardial inflammation by activating local angiotensin II and mineralocorticoid receptor systems and thereby aggravates cardiac hypertrophy and myocardial fibrosis, leading to systolic dysfunction, in hypertensive hearts. In addition, large BP variability induces the aggravation of arteriolosclerotic changes and ischemic cortical fibrosis in hypertensive kidney via local angiotensin II system. PMID:25544288

  7. Airways Hyperresponsiveness Following a Single Inhalation Exposure to Doxorubicin-Induced Heart Failure Prevents Airways Transition Metal-Rich Particulate Matter in Hypertensive Rats

    EPA Science Inventory

    Exposure to particulate matter (PM) air pollution results in airways hyperresponsiveness (AHR), however it also results in adverse cardiovascular effects, particularly in individuals with underlying cardiovascular disease. The impact of pre-existing cardiac deficit on PM-induced ...

  8. A single exposure to particulate or gaseous air pollution increases the risk of aconitine-induced cardiac arrythmia in hypertensive rats

    EPA Science Inventory

    Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

  9. Hypertension, a health economics perspective.

    PubMed

    Alcocer, Luis; Cueto, Liliana

    2008-06-01

    The economic aspects of hypertension are critical to modern medicine. The medical, economic, and human costs of untreated and inadequately controlled hypertension are enormous. Hypertension is distributed unequally and with iniquity in different countries and regions of the world. Treatment of hypertension requires an investment over many years to prolong disease-free quality years of life. The high prevalence and high cost of the disease impacts on the microeconomics and macroeconomics of countries and regions. The criteria used for inclusion in clinical guidelines for hypertension impact on the cost and cost/utility of diagnosis or treatment. PMID:19124418

  10. Mechanisms and drug therapy of pulmonary hypertension at high altitude.

    PubMed

    Scherrer, Urs; Allemann, Yves; Rexhaj, Emrush; Rimoldi, Stefano F; Sartori, Claudio

    2013-06-01

    Pulmonary vasoconstriction represents a physiological adaptive mechanism to high altitude. If exaggerated, however, it is associated with important morbidity and mortality. Recent mechanistic studies using short-term acute high altitude exposure have provided insight into the importance of defective vascular endothelial and respiratory epithelial nitric oxide (NO) synthesis, increased endothelin-1 bioavailability, and overactivation of the sympathetic nervous system in causing exaggerated hypoxic pulmonary hypertension in humans. Based on these studies, drugs that increase NO bioavailability, attenuate endothelin-1 induced pulmonary vasoconstriction, or prevent exaggerated sympathetic activation have been shown to be useful for the treatment/prevention of exaggerated pulmonary hypertension during acute short-term high altitude exposure. The mechanisms underpinning chronic pulmonary hypertension in high altitude dwellers are less well understood, but recent evidence suggests that they differ in some aspects from those involved in short-term adaptation to high altitude. These differences have consequences for the choice of the treatment for chronic pulmonary hypertension at high altitude. Finally, recent data indicate that fetal programming of pulmonary vascular dysfunction in offspring of preeclampsia and children generated by assisted reproductive technologies represents a novel and frequent cause of pulmonary hypertension at high altitude. In animal models of fetal programming of hypoxic pulmonary hypertension, epigenetic mechanisms play a role, and targeting of these mechanisms with drugs lowers pulmonary artery pressure. If epigenetic mechanisms also are operational in the fetal programming of pulmonary vascular dysfunction in humans, such drugs may become novel tools for the treatment of hypoxic pulmonary hypertension. PMID:23795732

  11. Circulatory effects of stress in essential hypertension.

    PubMed

    Andrén, L; Hansson, L

    1981-01-01

    Hemodynamics and plasma catecholamines were studied during mental arithmetics and cold pressor test in thirteen patients with essential hypertension. Blood pressure was significantly increased by both forms of "stress". Cold pressor test caused a significant increase in total peripheral resistance, while mental arithmetics increased heart rate and cardiac output significantly. Thus, different forms of "stress" can increase blood pressure by totally different hemodynamic mechanisms. Acute cardioselective and non-selective beta-receptor blockade did not affect the hemodynamic reaction pattern during cold pressor test. The increase in heart rate and cardiac output during mental arithmetics was blocked by non-selective but not with cardioselective beta-blockade. Both beta-blockers were, however, inefficient in preventing the blood pressure elevation induced by mental arithmetics. Plasma noradrenalin was significantly increased during mental arithmetics after both cardioselective and non-selective beta-blockade compared to placebo. During cold pressor test there was a significant increase in noradrenalin only after non-selective beta-blockade. Adrenalin in plasma was significantly increased only during mental arithmetics after cardioselective beta-blockade. The pathogenesis of essential hypertension is complex and still not fully understood. Both hereditary (1) and environmental factors such as salt intake (2) and stress (3,4,5) are probably of importance as risk factors for essential hypertension. Animal studies have shown that different forms of stress can produce permanent hypertension due to structural changes in the resistance vessels (6). Against this background we decided to investigate acute hemodynamic effects of two well-defined types of "stress", e.g. mental arithmetics and cold pressor test in patients with essential hypertension and to study if the hemodynamic reactions could be modified by cardioselective and non-selective beta-receptor blockade. Catecholamines in plasma were studied before, during and after "stress". PMID:7018187

  12. Pharmacologically induced release and modulation of /sup 3/H-norepinephrine (NE) from the isolated portal vein of the spontaneously hypertensive rat (SHR)

    SciTech Connect

    Zhang, S.Q.; Westfall, T.C.

    1986-03-05

    The purpose of the present study was to probe the mechanism for the enhancement of the field-stimulation induced release of /sup 3/H-NE from blood vessels of the SHR compared to normotensive rats. The results of two types of experiments are reported here. First, the effect of nicotine as well as tyramine in inducing the release of /sup 3/H-NE from the superfused portal vein was compared to field stimulation. Secondly, the modulatory effect of serotonin (5-HT) and methacholine (M) on the field stimulation induced release of /sup 3/H-NE was examined. In contrast to the enhancement of the field stimulation induced release of /sup 3/H-NE from the portal vein of the SHR compared to WKY, both nicotine and tyramine produced a similar release of NE from blood vessel obtained from both strains. The fractional release of /sup 3/H-NE to 10/sup -4/, 10/sup -3/ and 10/sup -2/M nicotine was 0.21, 0.67 and 45.5 from WKY and 0.14, 0.68 and 42.4 from SHR. The fractional release of /sup 3/H-NE to 10/sup -4/ and 10/sup -3/M tyramine was 6 and 17 from WKY compared to 7.5 and 17.5 from SHR. The inhibition of /sup 3/H-NE release from the portal vein by both 5-HT and M was similar in blood vessels obtained from SHR and WKY. These results are consistent with there being a defect in the exocytotic induced release of NE from noradrenergic neurons at the vascular neuroeffector junction.

  13. Hypertension in perspective

    PubMed Central

    Terpstra, W.F.; Zijlstra, F.

    2005-01-01

    Decisions about the management of hypertensive patients should not be based on the level of blood pressure alone, but also on the presence of other risk factors, target organ damage and cardiovascular and renal disease. The results of echocardiography and carotid ultrasonography aids in the stratification of absolute cardiovascular risk as recently advocated by the guidelines of the European Society of Hypertension 2003. Therefore, the detection of target organ damage by ultrasound techniques allows an accurate identification of high-risk patients. Cardiovascular risk stratification only based on a simple routine work-up can often underestimate overall risk, thus leading to a potentially inadequate therapeutic management especially of low-medium risk patients. PMID:25696486

  14. Hypertension in pregnancy.

    PubMed Central

    Anyaegbunam, A.; Edwards, C.

    1994-01-01

    Hypertension, which is the most common complication of pregnancy, is a leading cause of both maternal and perinatal morbidity. Advances in research related to hypertensive disorders in pregnancy have facilitated a better general understanding of the pathophysiologic processes associated with this disease. Strategies of prevention, early diagnosis, and newer treatments have contributed to a more favorable outcome for mothers and their babies. The exact cause of preeclampsia remains elusive; however, recent investigations suggest that endothelial cell injury due to free radical-mediated lipid peroxidation may be the initiator of the pathophysiologic events of preeclampsia. Future challenges in this area should include efforts to elucidate mechanisms involved in free radical cell-mediated vascular disturbances and antioxidant defenses. PMID:8040904

  15. Gestational pulmonary arterial hypertension

    PubMed Central

    Moll, Matthew; Payne, Julie G.; Tukey, Melissa H.

    2015-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a progressive disease marked by the irreversible pulmonary vascular changes of vasoconstriction, thrombosis, and proliferation of smooth muscle and endothelial cells. The untreated clinical course is characterized by progressive dyspnea and a median survival of less than 3 years. Many of these patients are of child-bearing age; however, pregnancy leads to physiologic changes that are particularly poorly tolerated in PAH, conferring a 30%–56% mortality. We present a case of PAH that spontaneously resolved after termination of pregnancy and recurred during each of two subsequent pregnancies. To our knowledge, this case is unique, because no cases of spontaneous resolution of idiopathic PAH have been reported in adults, nor have there been any reports of pulmonary hypertension that is isolated to the gestational period. PMID:26697182

  16. Captopril in essential hypertension

    PubMed Central

    Estrada, E. Rabinad; Morin, M. Ingelmo; Amenos, A. Martinez; Alsina, J.; Gorina, A. Balcells

    1982-01-01

    1 Forty-one patients with essential hypertension, stages I, II, and III, were treated with captopril alone or in combination with hydrochlorothiazide. Forty two percent were responsive to captopril alone, while the remaining 58% also required the diuretic. The need for the diuretic was related to the phase of hypertension. 2 There was no significant relation between drug response and plasma renin activity. Serum concentrations of creatinine and potassium remained normal, and there were no pathological changes in serum glucose, cholesterol, uric acid concentrations, erythrocyte count, packed cell volume, haemoglobin, or heart rate. 3 Captopril was well tolerated. One patient developed a rash and another ageusia, which disappeared spontaneously. A third, who was also taking allopurinol, developed leucopenia but it disappeared after treatment was withdrawn. There were no cases of proteinuria attributable to captopril; and proteinuria disappeared in four of five patients who were proteinuric before the start of treatment. 4 These findings suggest that doses of captopril of 150 mg to 300 mg (with or without a diuretic) may be adequate for controlling the blood pressure of most patients with essential hypertension. PMID:6753890

  17. Genetics Home Reference: Pulmonary arterial hypertension

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Pulmonary arterial hypertension On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed September 2012 What is pulmonary arterial hypertension? Pulmonary arterial hypertension is a progressive disorder characterized ...

  18. Exercise Appears Safe, Helpful for Pulmonary Hypertension

    MedlinePLUS

    ... 154487.html Exercise Appears Safe, Helpful for Pulmonary Hypertension Research review might reassure concerned cardiologists To use ... be beneficial and safe for people with pulmonary hypertension, researchers report. Pulmonary hypertension is a type of ...

  19. Hypertension produced by a high sodium diet in the borderline hypertensive rat (BHR).

    PubMed

    Lawler, J E; Sanders, B J; Chen, Y F; Nagahama, S; Oparil, S

    1987-01-01

    The effect of high dietary sodium (8%) on blood pressure in spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats was determined weekly by tail cuff plethysmography for one week of baseline and four weeks of diet. After 4 weeks, significant elevations in systolic blood pressure were found in SHR and BHR groups, but not in WKY. BHR studied an additional 4 weeks showed a further progression of hypertension, reaching levels nearly equal to control SHR. Direct measurement of arterial pressure in conscious animals in their home cage confirmed the elevation in pressure in both SHR and BHR groups. Metabolic studies revealed that the high sodium diet reduced body weight in SHR and BHR strains, but not in WKY. Although both urinary volumes and sodium excretion values were significantly lower in SHR and BHR compared with WKY, this effect disappeared when adjustments for body weight were made. Plasma norepinephrine determinations revealed a significant response to cold stress in all groups. Plasma epinephrine was elevated in all strains in response to cold stress; however, a consistent statistical elevation was seen only in WKY. The BHR is discussed as a model for determining the triggers responsible for environmentally-induced hypertension. PMID:3436073

  20. What constitutes controlled hypertension? Patient based comparison of hypertension guidelines.

    PubMed Central

    Fahey, T. P.; Peters, T. J.

    1996-01-01

    OBJECTIVES--To investigate and quantify the extent to which variations in guidelines influence assessment of control of hypertension. DESIGN--Cross sectional study. Selected patients had hypertension assessed as controlled or uncontrolled with guidelines from New Zealand, Canada, the United States, Britain, and the World Health Organisation. SETTING--18 general practices in Oxfordshire. SUBJECTS--876 patients with diagnosed hypertension and taking antihypertensive drugs. MAIN OUTCOME MEASURES--Proportion of patients with controlled hypertension according to each set of guidelines. RESULTS--The proportion of patients with controlled hypertension varied from 17.5% to 84.6% with the different guidelines after adjustment for the sampling method. All five sets of guidelines agreed on the classification for 31% (277) of the patients. The New Zealand guidelines calculate an absolute risk of a cardiovascular event. When this was taken as the standard half of the patients with uncontrolled hypertension by the United States criteria would be treated unnecessarily and 31% of those classified as having controlled hypertension by the Canadian guidelines would be denied beneficial treatment. CONCLUSIONS--Hypertension guidelines are inconsistent in their recommendations and need to make clear the absolute benefits and risks of treatment. PMID:8688763

  1. Carotid body potentiation during chronic intermittent hypoxia: implication for hypertension

    PubMed Central

    Del Rio, Rodrigo; Moya, Esteban A.; Iturriaga, Rodrigo

    2014-01-01

    Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH). It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB) chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14, and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS, and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function. PMID:25429271

  2. Qigong for Hypertension

    PubMed Central

    Xiong, Xingjiang; Wang, Pengqian; Li, Xiaoke; Zhang, Yuqing

    2015-01-01

    Abstract The purpose of this review was to evaluate the efficacy and safety of qigong for hypertension. A systematic literature search was performed in 7 databases from their respective inceptions until April 2014, including the Cochrane Library, EMBASE, PubMed, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, Wanfang database, and Chinese National Knowledge Infrastructure. Randomized controlled trials of qigong as either monotherapy or adjunctive therapy with antihypertensive drugs versus no intervention, exercise, or antihypertensive drugs for hypertension were identified. The risk of bias was assessed using the tool described in Cochrane Handbook for Systematic Review of Interventions, version 5.1.0. Twenty trials containing 2349 hypertensive patients were included in the meta-analysis. The risk of bias was generally high. Compared with no intervention, qigong significantly reduced systolic blood pressure (SBP) (weighted mean difference [WMD]?=??17.40?mm Hg, 95% confidence interval [CI] ?21.06 to ?13.74, P?hypertension. However, more rigorously designed randomized controlled trials with long-term follow-up focusing on hard clinical outcomes are required to confirm the results. PMID:25569652

  3. Mechanisms of hypertension in renal radiation

    SciTech Connect

    Juncos, L.; Cornejo, J.C.; Cejas, H.; Broglia, C. )

    1990-02-01

    This study was undertaken to investigate the role played by renal functional and structural changes in the development of radiation-induced hypertension. Four groups of rats were studied: (1) left kidney radiated, (2) sham procedure, (3) uninephrectomy followed 3 weeks later by radiation of the contralateral kidney, and (4) uninephrectomy followed by sham procedure 3 weeks later. All radiated rats became hypertensive at 12 weeks (p less than 0.05) and had higher protein excretion (p less than 0.05). In the presence of an intact contralateral kidney, radiation causes mild-to-moderate histological abnormalities, and therefore, creatinine clearance and water and sodium handling do not change. Plasma renin activity increased in this group (p less than 0.05). Radiated uninephrectomized rats showed decreased creatinine clearance (p less than 0.05), but renin activity remained unchanged. These rats developed severe histological abnormalities in glomeruli, interstitia, tubuli, and vessels resulting in increased sodium and water output. The average of individual tubular and interstitial scores correlated significantly with both water intake and output but not with sodium excretion. These studies suggest that in the presence of an intact kidney, renin is an important determinant in the development or maintenance of radiation hypertension, whereas in the absence of the contralateral kidney, severe histological changes and renal failure are prominent despite increased water intake and output. The more severe glomerular sclerosis and proteinuria in the latter model could be related to diminished renal mass.

  4. Obesity Associated Hypertension: New Insights into Mechanism

    PubMed Central

    2013-01-01

    With excess nutrition, the burden of obesity is a growing problem worldwide. The imbalance between energy intake and expenditure leads to variable disorders as all major risk factors for cardiovascular disease. There are many hypothetical mechanisms to explain obesity-associated hypertension. Activation of the RAAS is a key contributing factor in obesity. Particularly, the RAAS in adipose tissue plays a crucial role in adipose tissue dysfunction and obesity-induced inflammation. The phenotypic changes of adipocytes occur into hypertrophy and an inflammatory response in an autocrine and paracrine manner to impair adipocyte function, including insulin signaling pathway. Adipose tissue produce and secretes several molecules such as leptin, resistin, adiponectin, and visfatin, as well as cytokines such as TNF-?, IL-6, MCP-1, and IL-1. These adipokines are stimulated via the intracellular signaling pathways that regulate inflammation of adipose tissue. Inflammation and oxidative stress in adipose tissue are important to interact with the microvascular endothelium in the mechanisms of obesity-associated hypertension. Increased microvascular resistance raises blood pressure. Therefore, a regulatory link between microvascular and perivascular adipose tissue inflammation and adipokine synthesis are provided to explain the mechanism of obesity-associated hypertension. PMID:24627704

  5. The Immune System in Hypertension

    ERIC Educational Resources Information Center

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  6. Pre-hypertension: another ‘pseudodisease’?

    PubMed Central

    2013-01-01

    Hypertension is one of the most important and common cardiovascular risk factors. Defining the level at which blood pressure starts causing end-organ damage is challenging, and is not easily answered. The threshold of blood pressure defining hypertension has progressively been reduced over time, from systolic >160 mmHg to >150 mmHg, then to >140 mmHg; and now even blood pressures above 130 to 120 mmHg are labeled as ‘pre-hypertension’ by some expert committees. Are interest groups creating another ‘pseudodisease’ or is this trend scientifically justified? A recent meta-analysis published in BMC Medicine by Huang et al. clearly indicates that pre-hypertension (120 to 140/80 to 90 mmHg) is a significant marker of increased cardiovascular risk. This raises the question as to whether we now need to lower the threshold of ‘hypertension’ (as opposed to ‘pre-hypertension’) to >120/80 mmHg, redefining a significant proportion of currently healthy people as ‘patients’ with an established disease. These data need to be interpreted with some caution. It is controversial whether pre-hypertension is an independent risk factor or just a risk marker and even more controversial whether treatment of pre-hypertension will lower cardiovascular risk. Please see related research: http://www.biomedcentral.com/1741-7015/11/177. PMID:24229371

  7. Potential adverse interaction between aspirin and lisinopril in hypertensive rats.

    PubMed

    Dubey, K; Balani, D K; Pillai, K K

    2003-03-01

    The potential clinical effect of aspirin (ASA) in patients treated with angiotensin converting enzyme (ACE) inhibitors is debatable. Several studies have suggested that ASA attenuates the beneficial effects of ACE inhibitors in hypertension, congestive heart failure (CHF) or coronary artery disease (CAD) and have questioned the safety of using ASA concomitantly with these agents. The present study aims to investigate the possible interaction between ASA and ACE inhibitor in hypertensive rats. Hypertension was induced in adult male Wistar rats using Methylprednisolone (MP) 20 mg/kg per week s.c. for 2 weeks. The systolic blood pressure (SBP) was measured by noninvasive BP technique. The effect of Lisinopril (LS) 15 mg/kg per day and that of combination of LS and ASA; 100 and 25 mg/kg per day p.o. was studied on hypertension induced by glucocorticoid. Concurrent ASA treatment with LS did not hinder the hypotensive effect of LS at either dose. However ASA 100 mg/kg per day caused mortality in animals and produced massive cardiac necrosis and renal damage as evident from histopathology. Treatment with ASA 25 mg/kg per day caused lower mortality with variable effects on cardiac and renal tissues. These results indicate that ASA attenuates the beneficial effects of ACE inhibitor on survival in hypertensive rats and this effect was more pronounced at higher dose of ASA. PMID:12723895

  8. Dietary Approaches to Prevent Hypertension

    PubMed Central

    Bazzano, Lydia A.; Green, Torrance; Harrison, Teresa N.

    2015-01-01

    Elevated blood pressure arises from a combination of environmental and genetic factors and the interactions of these factors. A substantial body of evidence from animal studies, epidemiologic studies, meta-analyses, and randomized controlled trials has demonstrated that certain dietary patterns and individual dietary elements play a prominent role in the development of hypertension. Changes in diet can lower blood pressure, prevent the development of hypertension, and reduce the risk of hypertension-related complications. Dietary strategies for the prevention of hypertension include reducing sodium intake, limiting alcohol consumption, increasing potassium intake, and adopting an overall dietary pattern such as the DASH (Dietary Approaches to Stop Hypertension) diet or a Mediterranean diet. In order to reduce the burden of blood pressure-related complications, efforts that focus on environmental and individual behavioral changes that encourage and promote healthier food choices are warranted. PMID:24091874

  9. Exercise, the Brain, and Hypertension.

    PubMed

    Peri-Okonny, Poghni; Fu, Qi; Zhang, Rong; Vongpatanasin, Wanpen

    2015-10-01

    Exercise training is the cornerstone in the prevention and management of hypertension and atherosclerotic cardiovascular disease. However, blood pressure (BP) response to exercise is exaggerated in hypertension often to the range that raises the safety concern, which may prohibit patients from regular exercise. This augmented pressor response is shown to be related to excessive sympathetic stimulation caused by overactive muscle reflex. Exaggerated sympathetic-mediated vasoconstriction further contributes to the rise in BP during exercise in hypertension. Exercise training has been shown to reduce both exercise pressor reflex and attenuate the abnormal vasoconstriction. Hypertension also contributes to cognitive impairment, and exercise training has been shown to improve cognitive function through both BP-dependent and BP-independent pathways. Additional studies are still needed to determine if newer modes of exercise training such as high-intensity interval training may offer advantages over traditional continuous moderate training in improving BP and brain health in hypertensive patients. PMID:26341655

  10. The Anachronistic Terminology of Gestational Hypertension: Time for a Change.

    PubMed

    Clark, Steven L; Belfort, Michael A; Hankins, Gary D V

    2015-08-01

    Few conditions in medicine are plagued with as confusing and anachronistic terminology as the clinical variants of pregnancy-induced hypertension and preeclampsia. We propose a simple system of nomenclature that reflects both actual pathophysiology and standard 21st century medical terminology. Such a change would facilitate both rational, evidence-based clinical care, collaboration with other specialties, and research. PMID:26241417

  11. Blood Pressure Variability and Stress Management Training for Essential Hypertension

    ERIC Educational Resources Information Center

    Garcia-Vera, Maria Paz; Sanz, Jesus; Labrador, Francisco J.

    2004-01-01

    The purpose of this study was to determine whether stress management training reduces blood pressure (BP) variability in hypertensive patients. Previous literature suggests that cardiovascular risk is not only a function of BP levels, but also of BP variability, and this partially depends on changes induced by the stress of everyday life. The…

  12. Segmental portal hypertension.

    PubMed Central

    Madsen, M S; Petersen, T H; Sommer, H

    1986-01-01

    Isolated obstruction of the splenic vein leads to segmental portal hypertension, which is a rare form of extrahepatic portal hypertension, but it is important to diagnose, since it can be cured by splenectomy. In a review of the English literature, 209 patients with isolated splenic vein obstruction were found. Pancreatitis caused 65% of the cases and pancreatic neoplasms 18%, whereas the rest was caused by various other diseases. Seventy-two per cent of the patients bled from gastroesophageal varices, and most often the bleeding came from isolated gastric varices. The spleen was enlarged in 71% of the patients. A correct diagnosis in connection with the first episode of bleeding was made in only 49%; 22% were operated on because of gastrointestinal bleeding, but the cause of bleeding was not found. The diagnosis should be suspected in patients with gastroesophageal varices, but without signs of a liver disease, especially if isolated gastric varices are found. The diagnosis is confirmed by portography. Images FIG. 1. FIG. 2. PMID:3729585

  13. [Hypertension treated with isotetrandrine].

    PubMed

    Dong, H Y; Yao, C

    1991-02-01

    The antihypertensive effect of isotetrandrine (IT) has been studied, in 50 cases with hypertension with the cross-over experiment controlled with nitrendipine (NTP). The results of the study demonstrate that the antihypertensive efficacy of IT to the mild and moderate or phase I, II, III hypertension cases was definite. After ingestion of the single-dose 0.2 g of IT, BP fell at 30 min, the maximal fall in BP was observed at 4 h and duration of the action was sustained for 8 hours. After administration of daily dose 0.3-0.6 g of IT for 4 wk, the total response rate of all patients was 84%. Compared with NTP, the total response rate difference was not significant. During treatment, the heart rate was slightly decreased, the blood lipids and glucose were not influenced, the left ventricular functions were obviously improved, and the adverse effects were fewer and milder. The antihypertensive mechanism of it may be associated with the blocking calcium channel. PMID:2060056

  14. Immunosuppression with mycophenolate mofetil attenuates the development of hypertension and albuminuria in deoxycorticosterone acetate–salt hypertensive rats

    PubMed Central

    Boesen, E.I.; Williams, D.L.; Pollock, J.S.; Pollock, D.M.

    2013-01-01

    Summary Interplay between the immune system and renin angiotensin system is emerging as a crucial factor in the development and progression of hypertension. The current study aimed to determine the involvement of immune cells in the hypertension and renal injury produced by a non-angiotensin II-dependent form of hypertension, deoxycorticosterone acetate (DOCA)-salt induced hypertension in rats.Male Sprague-Dawley rats underwent uninephrectomy and either received a sustained release pellet of DOCA s.c. and 0.9% NaCl (saline) to drink, or received a placebo pellet and water to drink for 21 days. Additional groups of DOCA-saline and placebo-treated rats were treated concurrently with the immune suppressant mycophenolate mofetil (MMF; 30 mg.kg?1.d?1). Rats were placed in metabolic cages for 24 h urine collection prior to and at weekly intervals during the 21-day experimental period.MMF significantly attenuated development of hypertension in DOCA-saline rats (mean arterial pressure by telemetry of 146±7 versus 180±3 mmHg at day 18; P < 0.001), and of proteinuria (87±27 versus 305±63 mg/d at day 21) and albuminuria (51±15 versus 247±73 mg/d at day 21). Creatinine clearance was better preserved in MMF-treated DOCA-saline rats (0.74±0.07 ml/min) compared to untreated DOCA-saline rats (0.49±0.09 ml/min; P < 0.05), but was still significantly reduced compared to the placebo group (1.15±0.12 ml/min; P < 0.05). MMF treatment significantly attenuated the DOCA-salt induced rise in renal cortical T-lymphocyte and macrophage infiltration (P < 0.05).These data indicate immune cells play a deleterious role in both the hypertension and renal injury associated with DOCA-salt hypertension. PMID:20626757

  15. Hypertension and the pregnancy complicated by diabetes.

    PubMed

    Leguizamón, Gustavo F; Zeff, Natalia P; Fernández, Alberto

    2006-08-01

    Diabetes is a frequent complication of pregnancy. Type 1 diabetes is associated with an increased incidence of preeclampsia and pregnancy-induced hypertension. When renal dysfunction is present, the incidence of these complications is remarkably increased. White's class, poor glycemic control during the first half of pregnancy, and early blood pressure elevation are also independent risk factors for developing preeclampsia. Whether gestational diabetes increases the background incidence of preeclampsia is still debated. Because therapeutic interventions such as low-dose aspirin and antioxidants have not been shown to be effective, preventive measures rely on tight blood glucose control, as well as adequate blood pressure treatment. PMID:16879782

  16. Brainstem Hypoxia Contributes to the Development of Hypertension in the Spontaneously Hypertensive Rat

    PubMed Central

    Ang, Richard; Machhada, Asif; Kasymov, Vitaliy; Karagiannis, Anastassios; Hosford, Patrick S.; Mosienko, Valentina; Teschemacher, Anja G.; Vihko, Pirkko; Paton, Julian F. R.; Kasparov, Sergey

    2015-01-01

    Systemic arterial hypertension has been previously suggested to develop as a compensatory condition when central nervous perfusion/oxygenation is compromised. Principal sympathoexcitatory C1 neurons of the rostral ventrolateral medulla oblongata (whose activation increases sympathetic drive and the arterial blood pressure) are highly sensitive to hypoxia, but the mechanisms of this O2 sensitivity remain unknown. Here, we investigated potential mechanisms linking brainstem hypoxia and high systemic arterial blood pressure in the spontaneously hypertensive rat. Brainstem parenchymal PO2 in the spontaneously hypertensive rat was found to be ?15 mm?Hg lower than in the normotensive Wistar rat at the same level of arterial oxygenation and systemic arterial blood pressure. Hypoxia-induced activation of rostral ventrolateral medulla oblongata neurons was suppressed in the presence of either an ATP receptor antagonist MRS2179 or a glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol, suggesting that sensitivity of these neurons to low PO2 is mediated by actions of extracellular ATP and lactate. Brainstem hypoxia triggers release of lactate and ATP which produce excitation of C1 neurons in vitro and increases sympathetic nerve activity and arterial blood pressure in vivo. Facilitated breakdown of extracellular ATP in the rostral ventrolateral medulla oblongata by virally-driven overexpression of a potent ectonucleotidase transmembrane prostatic acid phosphatase results in a significant reduction in the arterial blood pressure in the spontaneously hypertensive rats (but not in normotensive animals). These results suggest that in the spontaneously hypertensive rat, lower PO2 of brainstem parenchyma may be associated with higher levels of ambient ATP and l-lactate within the presympathetic circuits, leading to increased central sympathetic drive and concomitant sustained increases in systemic arterial blood pressure. PMID:25712724

  17. Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats

    PubMed Central

    dos Santos Pereira, Maurício; Sathler, Matheus Figueiredo; Valli, Thais da Rosa; Marques, Richard Souza; Ventura, Ana Lucia Marques; Peccinalli, Ney Ronner; Fraga, Mabel Carneiro; Manhães, Alex C.; Kubrusly, Regina

    2015-01-01

    Methylphenidate (MPD) is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i) to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii) to establish the neurochemical consequences of short- (24 hours) and long-term (10 days) MPD withdrawal after a subchronic treatment (30 days) with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally), (iii) to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC) and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p.) presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult life. PMID:26509840

  18. Weight control in the management of hypertension. World Hypertension League.

    PubMed Central

    1989-01-01

    This article, which includes a brief description of the mechanisms and some epidemiological findings in obesity and high blood pressure, sums up present knowledge on a complex subject and provides guidance to medical practitioners on the management of obese hypertensive patients. Weight reduction, together with drug therapy in severe and moderate hypertension, and other non-pharmacological methods and continuing observation in mild hypertension are the essential measures to be applied. In addition to the lowering of blood pressure, weight loss offers several other metabolic and haemodynamic benefits. PMID:2670295

  19. Hypertension in Patients with Cancer

    PubMed Central

    de Souza, Vinicius Barbosa; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade

    2015-01-01

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality. PMID:25742420

  20. Dermatoglyphics in hypertension: a review.

    PubMed

    Wijerathne, Buddhika T B; Meier, Robert J; Agampodi, Thilini C; Agampodi, Suneth B

    2015-01-01

    Hypertension is a major contributor to the global burden of disease and mortality. A major medical advancement would be a better means to ascertain which persons are at higher risk for becoming hypertensive beforehand. To that end, there have been a number of studies showing that certain dermatoglyphic markers are associated with hypertension. This association could be explained if the risk toward developing hypertension later on in life is somehow connected with fetal development of dermatoglyphics. It would be highly valuable from a clinical standpoint if this conjecture could be substantiated since dermatoglyphic markers could then be used for screening out individuals who might be at an elevated risk of becoming hypertensive. The aim of this review was to search for and appraise available studies that pertain to the association between hypertension and dermatoglyphics.A systematic literature search conducted using articles from MEDLINE (PubMed), Trip, Cochran, Google scholar, and gray literature until December 2014. Of the 37 relevant publications, 17 were included in the review. The review performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.This review showed a fairly consistent finding of an increased frequency of whorl patterns along with a higher mean total ridge count in digital dermatoglyphic results in hypertensive samples compared to controls. However, it was imperative to discuss several limitations found in the studies that could make this association as yet unsettled. PMID:26265377

  1. Hypertension in the elderly: some practical considerations.

    PubMed

    Chaudhry, Kashif N; Chavez, Patricia; Gasowski, Jerzy; Grodzicki, Tomasz; Messerli, Franz H

    2012-10-01

    Data from randomized controlled trials suggest that treating hypertension in the elderly, including octogenarians, may substantially reduce the risk of cardiovascular disease and death. However, treatment remains challenging because of comorbidities and aging-related changes. We present common case scenarios encountered while managing elderly patients with hypertension, including secondary hypertension, adverse effects of drugs, labile hypertension, orthostatic hypotension, and dementia. PMID:23027728

  2. Benign intracranial hypertension

    PubMed Central

    Crowther, Edward R

    1993-01-01

    Benign intracranial hypertension (BIH) is a syndrome characterized by papilledema and elevated intracranial pressure in the absence of hydrocephalus or intracranial mass. The condition is found most often in obese females in the fourth decade of life. Etiology remains unclear but a wide variety of medications, disease states and altered physiology have been associated with its onset. The complaints of headache and disturbed visual acuity are those directly related to increased intracranial pressure. The most serious sequelae of untreated BIH is permanent, partial visual deficit. Early diagnosis and referral is important if visual loss is to be minimized or prevented. The case of a 33-year-old female with BIH presenting to a chiropractic office is described. The limited role of the chiropractor in diagnosis and monitoring of the condition is reviewed. ImagesFigure 1Figure 1

  3. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ? 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ? 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments. PMID:23829793

  4. Collateral Pathways in Portal Hypertension

    PubMed Central

    Sharma, Malay; Rameshbabu, Chittapuram S.

    2012-01-01

    Presence of portosystemic collateral veins (PSCV) is common in portal hypertension due to cirrhosis. Physiologically, normal portosystemic anastomoses exist which exhibit hepatofugal flow. With the development of portal hypertension, transmission of backpressure leads to increased flow in these patent normal portosystemic anastomoses. In extrahepatic portal vein obstruction collateral circulation develops in a hepatopetal direction and portoportal pathways are frequently found. The objective of this review is to illustrate the various PSCV and portoportal collateral vein pathways pertinent to portal hypertension in liver cirrhosis and EHPVO. PMID:25755456

  5. Myelofibrosis, splenomegaly, and portal hypertension.

    PubMed

    Jacobs, P; Maze, S; Tayob, F; Harries-Jones, E P

    1985-01-01

    A patient with chronic myelofibrosis and massive splenomegaly developed portal hypertension with haematemesis occurring from radiologically proven oesophageal varices. Transjugular liver biopsy showed only myeloid metaplasia, and radiological evaluation of the portal vascular system was undertaken to establish a diagnosis of hyperkinetic portal hypertension as a basis for therapeutic splenectomy. The alternative and rare situation of splenic and portal vein occlusion was demonstrated and therefore removal of the spleen was not an appropriate procedure for relief of portal hypertension. The variceal bleeding was successfully controlled with injection sclerotherapy. PMID:3934908

  6. 5-Hydroxytryptamine lowers blood pressure in normotensive and hypertensive rats.

    PubMed

    Diaz, Jessica; Ni, Wei; Thompson, Janice; King, Andrew; Fink, Gregory D; Watts, Stephanie W

    2008-06-01

    Arterial hyper-responsiveness to 5-hydroxytryptamine (5-HT) is a hallmark of hypertension, and plasma levels of free 5-HT are elevated in hypertension. We hypothesized that chronic administration of 5-HT would cause blood pressure to 1) rise in normotensive rats and 2) rise significantly more in hypertensive rats. The deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rat were used. Animals were implanted with minipumps that delivered 5-HT (or vehicle) at a rate of 25 microg/kg/min for 7 days. Free plasma 5-HT was elevated significantly by this protocol. Within 48 h, mean arterial blood pressure measured telemetrically decreased in sham (106 +/- 2 to 83 +/- 2 mm Hg) and in DOCA-salt hypertensive (166 +/- 9 to 112 +/- 3 mm Hg) rats; vehicle did not change blood pressure in either group. Ganglionic blockade (hexamethonium) reduced blood pressure to a greater magnitude in DOCA vehicle-administered rats (peak fall arterial pressure, 91 +/- 14 mm Hg) compared with DOCA 5-HT-administered rats (40 +/- 6 mm Hg). Maximal acetylcholine-induced (NO-dependent) relaxation in phenylephrine-contracted aortic strips was greater in 5-HT-administered (69.2 +/- 9.1% relaxation) versus vehicle-administered (39.7 +/- 14.2%) DOCA rats; aortic endothelial cell nitric oxide synthase expression was higher in the 5-HT- versus vehicle-administered DOCA-salt rats. In normotensive and DOCA-salt hypertensive rats, the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine (0.5 g/l in water) prevented the fall in blood pressure to 5-HT. We conclude that chronic exogenous 5-HT reduces blood pressure in normotensive and hypertensive rats through mechanisms critically dependent on NOS. PMID:18305011

  7. Clinical overview of hypertensive crisis in children.

    PubMed

    Yang, Wen-Chieh; Lin, Mao-Jen; Chen, Chun-Yu; Wu, Han-Ping

    2015-06-16

    Hypertensive emergencies and hypertensive urgencies in children are uncommonly encountered in the pediatric emergency department and intensive care units, but the diseases are potentially a life-threatening medical emergency. In comparison with adults, hypertension in children is mostly asymptomatic and most have no history of hypertension. Additionally, measuring accurate blood pressure values in younger children is not easy. This article reviews current concepts in pediatric patients with severe hypertension. PMID:26090371

  8. Clinical overview of hypertensive crisis in children

    PubMed Central

    Yang, Wen-Chieh; Lin, Mao-Jen; Chen, Chun-Yu; Wu, Han-Ping

    2015-01-01

    Hypertensive emergencies and hypertensive urgencies in children are uncommonly encountered in the pediatric emergency department and intensive care units, but the diseases are potentially a life-threatening medical emergency. In comparison with adults, hypertension in children is mostly asymptomatic and most have no history of hypertension. Additionally, measuring accurate blood pressure values in younger children is not easy. This article reviews current concepts in pediatric patients with severe hypertension. PMID:26090371

  9. Psychological symptoms and intermittent hypertension following acute microwave exposure

    SciTech Connect

    Forman, S.A.; Holmes, C.K.; McManamon, T.V.; Wedding, W.R.

    1982-11-01

    Two men who were accidently, acutely irradiated with X-band microwave radiation have been followed up clinically for 12 months. Both men developed similar psychological symptoms, which included emotional lability, irritability, headaches, and insomnia. Several months after the incidents, hypertension was diagnosed in both patients. No organic basis for the psychological problems could be found nor could any secondary cause for the hypertension. A similar syndrome following microwave exposure has been described by the East Europeans. The two cases we report, with comparable subjective symptoms and hypertension following a common exposure, provide further strong, circumstantial evidence of cause and effect. A greater knowledge of the mechanisms involved in bioeffects which may be induced by radiofrequency and microwave radiation is definitely needed.

  10. Arsenic and diabetes and hypertension in human populations: A review

    SciTech Connect

    Chen, C.-J. Wang, S.-L.; Chiou, J.-M.; Tseng, C.-H.; Chiou, H.-Y.; Hsueh, Y.-M.; Chen, S.-Y.; Wu, M.-M.; Lai, M.-S.

    2007-08-01

    Long-term exposure to ingested arsenic from drinking water has been well documented to be associated with an increased risk of diabetes mellitus and hypertension in a dose-response relationship among residents of arseniasis-endemic areas in southwestern Taiwan and Bangladesh. An increased risk of self-reported hypertension but not diabetes was reported in a community-based study of residents who consumed drinking water with a low level of arsenic. Increased glycosylated hemoglobin level and systolic blood pressure were observed in workers occupationally exposed to arsenic. Inconsistent findings of arsenic and diabetes in occupational studies may result from the healthy worker effect and the variation in exposure measurement, age composition, number of patients, accuracy in diagnosis and classification of underlying causes of death, competing causes of death, and method to detect diabetes. The dose-response relationship and toxicological mechanisms of arsenic-induced diabetes and hypertension need further elucidation.

  11. Increased albumin permeation in eyes, aorta, and kidney of hypertensive rats fed galactose

    SciTech Connect

    Tilton, R.G.; LaRose, L.; Chang, K.; Weigel, C.J.; Williamson, J.R.

    1986-03-01

    These experiments were undertaken to determine whether ingestion of galactose increases albumin permeation in the vasculature of hypertensive rats. 50% dextrin (control) or 50% galactose diets were fed to unilaterally nephrectomized, male Sprague-Dawley rats weighing 200 g. Hypertension (systolic pressure >175 mmHg) was induced by weekly IM injections of 25 mg/kg DOCA and 1% saline drinking water; 3 months later /sup 125/I-albumin permeation was assessed in whole eyes, aorta and kidneys. /sup 125/I-albumin permeation was significantly increased in all 3 tissues of hypertensive rats (n = 9) vs controls (n = 9): aorta (3.30 +/- 0.19 (SD) vs 2.87 +/- 0.14), eye (3.15 +/- 0.14 vs 2.59 +/- 0.11), and kidney (6.58 +/- 0.63 vs 3.85 +/- 0.50). Albumin permeation was increased still further in hypertensive rats fed the galactose diet (n = 8): aorta (3.75 +/- 0.38), eye (3.82 +/- 0.17), and kidney (10.74 +/- 3.13). Hypertension +/- galactose feeding had no effect on albumin permeation in lung, skin, or brain. These findings indicate that: (1) hypertension increases albumin permeation in vessels affected by diabetic vascular diseases, and 2) hypertension-induced increases in albumin permeation are increased still further by galactose ingestion, presumably mediated by imbalances in polyol/insitol metabolism (analogous to those induced by diabetes) independent of hyperglycemia and/or insulinopenia.

  12. In vivo hypertensive arterial wall uptake of radiolabeled liposomes

    SciTech Connect

    Hodis, H.N.; Amartey, J.K.; Crawford, D.W.; Wickham, E.; Blankenhorn, D.H. )

    1990-06-01

    Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with (111In)nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.

  13. C-reactive protein in hypertensive disorders in pregnancy.

    PubMed

    Paternoster, Delia M; Fantinato, Sara; Stella, Andrea; Nanhornguè, Kimta Ngaradoumbe; Milani, Massimo; Plebani, Mario; Nicolini, Umberto; Girolami, Antonio

    2006-07-01

    Hypertension is the most frequent medical complication of pregnancy. A recent report demonstrates the flogistic pathogenesis of pregnancy-induced hypertension. Because C-reactive protein (CRP) is a marker of inflammation, it can be used in the differential diagnosis of hypertensive disorders of pregnancy. A total of 322 pregnant women at 24 to 32 weeks' gestation were enrolled. The control group (A) comprised 190 women. Sixty-three women had preeclampsia (PE, group B), 31 women presented transient hypertension (TH, group C), 19 had HELLP syndrome (HS, group D) and 19 had chronic hypertension (CH, group E). CRP serum concentrations were significantly higher in groups B, C, and D in comparison with the group A. In the whole population, systolic and diastolic pressure value inversely correlate with weight at delivery and weeks of gestation at delivery. CPR levels in patients with PE and HS inversely correlate with birth weight and gestational week at delivery. Normal plasma levels of CRP may be an important marker of differential diagnosis between TH and CH. In TH, PE, and HS, CRP levels were higher than in the control and CH groups, suggesting that inflammation may be the common pathogenetic cause of TH and PE. Finally CRP levels in preeclampsia are believed to correlate with preeclamptic process severity. PMID:16959687

  14. [Surgically curable hypertension (author's transl)].

    PubMed

    Gilloz, A; Tostain, J; Richard, A; Peyrard, A; Drogue, M

    A case of hypertension was cured by simultaneous surgical treatment of an obstructive urolithiasis associated with a pheochromocytoma. Primary devascularization of the adrenal tumor, reducing blood pressure and cardiac rhythm variations was allowed by preoperative arteriography. PMID:6275533

  15. Intracranial Hypertension: Medication and Surgery

    MedlinePLUS

    ... http://www.ihrfoundation.org/hypertension/info/C172 Surgery Optic Nerve Fenestration When sight is at risk and drug therapy has been unsuccessful, an optic nerve fenestration (also called an optic nerve sheath ...

  16. Schistosomiasis-associated pulmonary hypertension

    PubMed Central

    Mocumbi, Ana Olga H.; Kim, Nick H.; Mandel, Jess

    2014-01-01

    Abstract Schistosomiasis, a parasite-borne disease, is highly prevalent in Africa and Asia; it is estimated that close to 20 million people worldwide have a severe form of the disease. The chronic form can affect the gastrointestinal system and lead to hepatosplenic disease, and it may cause cardiopulmonary complications, including pulmonary hypertension. The exact pathogenesis of schistosomiasis-associated pulmonary hypertension (Sch-PH) remains unclear, although several mechanisms, including parasitic arterial embolization, pulmonary arteriopathy, and portopulmonary hypertension–like pathophysiology, have been suggested. The immunopathology of the disease is also unclear, although there are similarities with the immunology of idiopathic pulmonary arterial hypertension (PAH). Finally, the treatment of Sch-PH has not been well studied. There is some evidence on treating the underlying infection, with unclear effect on Sch-PH, and advanced PAH therapies are now being suggested, but more studies are needed to confirm their efficacy. PMID:25610596

  17. Hypertension in the metabolic syndrome: summary of the new position statement of the European Society of Hypertension.

    PubMed

    Redon, Josep; Cífková, Renata; Narkiewicz, Krzysztof

    2009-04-01

    Arterial hypertension is often part of a larger constellation of anthropometric and metabolic abnormalities that includes abdominal (or visceral) obesity, characteristic dyslipidemia (low high-density lipoprotein cholesterol and high triglycerides), glucose intolerance, insulin resistance and hyperuricemia. Using Adult Treatment Panel III criteria, prevalence is higher than in the general population and the metabolic syndrome (MS) can be found in as many as one third of patients. In hypertensives with MS, a high prevalence of hypertension-induced target organ damage and a negative prognostic value have been described. Dietary advice and life style changes should be strongly recommended and prompt pharmacologic treatment is required to control high blood pressure and to reduce risk. The effect of particular antihypertensive drugs on other components of the MS is an important clinical issue with consequences for the success of the treatment. PMID:19413186

  18. Tight junction disruption of blood-brain barrier in white matter lesions in chronic hypertensive rats.

    PubMed

    Fan, Yuhua; Yang, Xian; Tao, Yuqian; Lan, Linfang; Zheng, Lu; Sun, Jian

    2015-12-01

    Tight junctions (TJs) are the most important structure of the blood-brain barrier (BBB). Studies have shown that triggering of white matter lesions (WMLs) may be related to a BBB dysfunction, but rarely have studies observed the progressive changes in TJs longitudinally. In our present study, the ultrastructure of TJs was observed using a transmission electron microscope in Stroke-prone Renalvascular Hypertensive Rats. Western blotting was used to detect TJ-related proteins zonula occludens-1 and occludin. The results showed that in Stroke-prone Renalvascular Hypertensive Rats, the severity of WMLs increased gradually. TJs was destroyed gradually 8 weeks after hypertension. The levels of zonula occludens-1 and occludin also decreased gradually. These data suggested that long-term hypertension may contribute toward the gradual disruption of TJs of BBB and induce WMLs in chronic hypertensive rats. PMID:26426859

  19. Rapid hypertensinogenic effect of lead: studies in the spontaneously hypertensive rat

    SciTech Connect

    Nakhoul, F.; Kayne, L.H.; Brautbar, N.; Hu, M.S.; McDonough, A.; Eggena, P.; Golub, M.S.; Berger, M.; Chang, C.T.; Jamgotchian, N. )

    1992-01-01

    Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile response of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na(+)-K(+)-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na(+)-K(+)-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.

  20. Hypertensive disorders of pregnancy and maternal and foetal outcome: a case controlled study.

    PubMed

    Yadav, S; Saxena, U; Yadav, R; Gupta, S

    1997-10-01

    A case controlled prospective study of 250 cases of hypertension complicating pregnancy (study group) and 400 normal pregnant women (control group) was carried out to determine the effect of hypertension on maternal and foetal outcome. Pregnancy induced hypertension was present in 96% cases and chronic hypertension in 4% cases. Preterm delivery (28.8% versus 3%), labour induction rate (52.8% versus 3.25%), caesarean section rate (14.8% versus 3.5%), stillbirth rate (4.8% versus 0.25%) and overall perinatal mortality rate (14.8% versus 1%) were higher in study group compared to controls. In study group (40%) babies required special nursery care compared to controls (6.75%). From these results it can be concluded that maternal hypertension is associated with adverse pregnancy outcome. PMID:9567600

  1. Portopulmonary hypertension: from diagnosis to treatment.

    PubMed

    Giusca, Sorin; Jinga, Mariana; Jurcut, Ciprian; Jurcut, Ruxandra; Serban, Marinela; Ginghina, Carmen

    2011-10-01

    Portopulmonary hypertension is a form of pulmonary arterial hypertension that has gained interest in recent years with the development of liver transplantation techniques and new pulmonary vasodilator therapies. Portopulmonary hypertension is defined as pulmonary artery hypertension associated with portal hypertension with or without advanced hepatic disease. Echocardiography plays a major role in screening for portopulmonary hypertension but right heart catheterization remains the gold standard for diagnosis. The treatment of patients with portopulmonary hypertension consists of general measures that apply to all patients that carry the diagnosis of pulmonary hypertension and specific vasodilator therapies. These new therapies showed encouraging results in patients who would otherwise have a contraindication for liver transplantation. The review presents a summary of the current knowledge on the epidemiology, diagnosis, treatment and prognosis of patients with portopulmonary hypertension. PMID:21925050

  2. Induction of hypertension blunts baroreflex inhibition of vasopressin neurons in the rat.

    PubMed

    Han, Su Young; Bouwer, Gregory T; Seymour, Alexander J; Korpal, Aaron K; Schwenke, Daryl O; Brown, Colin H

    2015-11-01

    Vasopressin secretion from the posterior pituitary gland is determined by action potential discharge of hypothalamic magnocellular neurosecretory cells. Vasopressin is a potent vasoconstrictor, but vasopressin levels are paradoxically elevated in some patients with established hypertension. To determine whether vasopressin neurons are excited in hypertension, extracellular single-unit recordings of vasopressin neurons from urethane-anaesthetized Cyp1a1-Ren2 rats with inducible angiotensin-dependent hypertension were made. The basal firing rate of vasopressin neurons was higher in hypertensive Cyp1a1-Ren2 rats than in non-hypertensive Cyp1a1-Ren2 rats. The increase in firing rate was specific to vasopressin neurons because oxytocin neuron firing rate was unaffected by the induction of hypertension. Intravenous injection of the ?1 -adrenoreceptor agonist, phenylephrine (2.5 ?g/kg), transiently increased mean arterial blood pressure to cause a baroreflex-induced inhibition of heart rate and vasopressin neuron firing rate (by 52 ± 9%) in non-hypertensive rats. By contrast, intravenous phenylephrine did not inhibit vasopressin neurons in hypertensive rats, despite a similar increase in mean arterial blood pressure and inhibition of heart rate. Circulating angiotensin II can excite vasopressin neurons via activation of afferent inputs from the subfornical organ. However, the increase in vasopressin neuron firing rate and the loss of inhibition by intravenous phenylephrine were not blocked by intra-subfornical organ infusion of the angiotensin AT1 receptor antagonist, losartan. It can be concluded that increased vasopressin neuron activity at the onset of hypertension is driven, at least in part, by reduced baroreflex inhibition of vasopressin neurons and that this might exacerbate the increase in blood pressure at the onset of hypertension. PMID:26342194

  3. Paranormal healing and hypertension

    PubMed Central

    Beutler, Jaap J; Attevelt, Johannes T M; Schouten, Sybo A; Faber, Joop A J; Mees, Evert J Dorhout; Geijskes, Gijsbert G

    1988-01-01

    A prospective randomised trial was carried out to see whether paranormal healing by laying on of hands might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal, psychological, or placebo factor. Patients were randomised to three treatment groups: paranormal healing by laying on of hands (n=40), paranormal healing at a distance (n=37), and no paranormal healing (controls; n=38). Healing at a distance and no paranormal healing were investigated double blind. Systolic and diastolic blood pressures were significantly reduced in all three groups at week 15 (mean reduction (95% confidence interval) 17·1 (14·0 to 20·2)/8·3 (6·6 to 10·0) mm Hg). Only the successive reductions in diastolic blood pressures among the groups from week to week were significantly different. Each week diastolic pressure was consistently lower (average 1·9 mm Hg) after healing at a distance compared with control, but on paired comparison these differences were not significant. Probably week to week variations among the groups accounted for any differences noted. In this study no treatment was consistently better than another and the data cannot therefore be taken as evidence of a paranormal effect on blood pressure. Probably the fall in blood pressure in all three groups either was caused by the psychosocial approach or was a placebo effect of the trial itself. PMID:3134082

  4. Developmental programming and hypertension

    PubMed Central

    Nuyt, Anne Monique; Alexander, Barbara T.

    2009-01-01

    Purpose of review There is a growing body of evidence linking adverse events or exposures during early life and adult-onset diseases. After important epidemiological studies from many parts of the world, research now focuses on mechanisms of organ dysfunction and on refining the understanding of the interaction between common elements of adverse perinatal conditions, such as nutrition, oxidants, and toxins exposures. This review will focus on advances in our comprehension of developmental programming of hypertension. Recent findings Recent studies have unraveled important mechanisms of oligonephronia and impaired renal function, altered vascular function and structure as well as sympathetic regulation of the cardiovascular system. Furthermore, interactions between prenatal insults and postnatal conditions are the subject of intensive research. Prematurity vs. intrauterine growth restriction modulate differently programming of high blood pressure. Along with antenatal exposure to glucocorticoids and imbalanced nutrition, a critical role for perinatal oxidative stress is emerging. Summary While the complexity of the interactions between antenatal and postnatal influences on adult blood pressure is increasingly recognized, the importance of postnatal life in (positively) modulating developmental programming offers the hope of a critical window of opportunity to reverse programming and prevent or reduce related adult-onset diseases. PMID:19434052

  5. Angiotensin II-related hypertension and eye diseases

    PubMed Central

    Marin Garcia, Pablo Jesus; Marin-Castaño, Maria Encarna

    2014-01-01

    Systemic vascular disease, especially hypertension, has been suspected as a risk factor for some eye diseases including, diabetic retinopathy and age-related macular degeneration. Hypertension can contribute to chronic diseases by hemodynamic injury and/or cellular actions induced by hypertension-related hormones or growth factors. Among the most important is Angiotensin II (Ang II), which controls blood pressure and induces different cellular functions that may be dependent or independent of its effect on blood pressure. Importantly, as is true for heart, kidney and other organs, the renin-angiotensin system (RAS) is present in the eye. So, even in the absence of hypertension, local production of Ang II could be involved in eye diseases. The goal of this manuscript is to review the most relevant scientific evidence supporting the role of the RAS activation, in the development of age-related macular degeneration and diabetic retinopathy, and highlight the importance of Ang II in the etiology of these diseases. PMID:25276298

  6. Surgical Treatment of Cervical Spondylotic Myelopathy Associated Hypertension—A Retrospective Study of 309 Patients

    PubMed Central

    Jia, Wen-yu; Wang, Xia; Chen, Bin; Shahbaz, Muhammad; Nie, Lin; Cheng, Lei

    2015-01-01

    Hypertension is the most prevalent cardiovascular disease, and various risk factors are known to be involved in it. Cervical spondylotic myelopathy (CSM) is the most common non-traumatic cause of myelopathy, which displays neurological symptoms and may induce systemic symptoms. To date, it is still unknown whether CSM is associated with hypertension, and if so, whether the decompression operations can attenuate CSM associated hypertension. Here, a total of 309 patients with CSM who received anterior or posterior decompression surgery were enrolled as subjects. Blood pressure measurements were performed before and within one week after the surgery. Among the 309 subjects, 144 (46.6%) of them exhibited hypertension before surgery, a significantly higher ratio than that of the whole population. One week after surgery, blood pressure of 106 (73.6%) patients turned back to normal. Blood pressure of another 37(25.7%) patients decreased with different degrees, although still higher than normal. Moreover, it appears that both approaches were effective in improving blood pressure, while the posterior approach was more effective in decreasing systolic blood pressure. We speculate this type of hypertension might result from hyperactivity of sympathetic nervous system as the heart rate of these patients decreased after surgery as well. Collectively, compression of spinal cord in CSM patients might be associated with hypertension, and decompression surgery largely attenuated this type of hypertension. These findings prove CSM to be a potential associated factor of high blood pressure and may shed light on therapies of hypertension in clinics. PMID:26193469

  7. Ace gene dosage influences the development of renovascular hypertension.

    PubMed

    Ceroni, Alexandre; Moreira, Edson D; Mostarda, Cristiano T; Silva, Gustavo J J; Krieger, Eduardo M; Irigoyen, Maria C

    2010-04-01

    1. Clinical and experimental evidence highlights the importance of the renin-angiotensin system in renovascular hypertension. Furthermore, genetic factors affecting angiotensin-converting enzyme (ACE) could influence the development of renovascular hypertension. 2. To test the effect of small gene perturbations on the development of renovascular hypertension, mice harbouring two or three copies of the Ace gene were submitted to 4 weeks of two-kidney, one-clip (2K1C) hypertension. Blood pressure (BP), cardiac hypertrophy, baroreflex sensitivity and blood pressure and heart rate variability were assessed and compared between the different groups. 3. The increase in BP induced by 2K1C was higher in mice with three copies of the Ace gene compared with mice with only two copies (46 vs 23 mmHg, respectively). Moreover, there was a 3.8-fold increase in the slope of the left ventricle mass/BP relationship in mice with three copies of the Ace gene. Micewith three copies of the Ace gene exhibited greater increases in cardiac and serum ACE activity than mice with only two copies of the gene. Both baroreflex bradycardia and tachycardia were significantly depressed in mice with three copies of the Ace gene after induction of 2K1C hypertension. The variance in basal systolic BP was greater in mice with three copies of the Ace gene after 2K1C hypertension compared with those with only two copies of the gene (106 vs 54%, respectively). In addition, the low-frequency component of the pulse interval was higher mice with three copies of the Ace gene after 2K1C hypertension compared with those with only two (168 vs 86%, respectively). Finally, in mice with three copies of the Ace gene, renovascular hypertension induced a 6.1-fold increase in the sympathovagal balance compared with a 3.2-fold increase in mice with only two copies of the gene. 4. Collectively, these data provide direct evidence that small genetic disturbances in ACE levels per se have an influence on haemodynamic, cardiac mass and autonomic nervous system responses in mice under pathological perturbation. PMID:19930431

  8. Diagnosis and treatment of hypertension in children.

    PubMed

    Lurbe, Empar; Álvarez, Julio; Redon, Josep

    2010-12-01

    Hypertension is a global problem, affecting both developed and developing nations. In children and adolescents, hypertension has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiologic and clinical research. Childhood hypertension is often asymptomatic and is easily missed, even by health professionals. Target organ damage is detectable in children and adolescents. Management of hypertension includes lifestyle changes and pharmacologic treatment. In the case of secondary hypertension, pharmacologic treatment usually is required. In essential hypertension, assessment of early organ damage provides a useful tool for treatment decisions. PMID:20872099

  9. OLIGOCLONAL CD8+ T CELLS PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF HYPERTENSION

    PubMed Central

    Trott, Daniel W.; Thabet, Salim R; Kirabo, Annet; Saleh, Mohamed A.; Itani, Hana; Norlander, Allison E; Wu, Jing; Goldstein, Anna; Arendshorst, William J; Madhur, Meena S; Chen, Wei; Li, Chung-I; Shyr, Yu; Harrison, David G

    2014-01-01

    Recent studies have emphasized a role of adaptive immunity, and particularly T cells, in the genesis of hypertension. We sought to determine the T cell subtypes that contribute to hypertension and renal inflammation in angiotensin II-induced hypertension. Using T cell receptor (TCR) spectratyping to examine TCR usage we demonstrated that CD8+ cells, but not CD4+ cells, in the kidney exhibited altered TCR transcript lengths in V?3, 8.1 and 17 families in response to angiotensin II-induced hypertension. Clonality was not observed in other organs. The hypertension caused by angiotensin II in CD4?/? and MHCII?/? mice was similar to that observed in WT mice, while CD8?/? mice and OT1xRAG-1?/? mice, which have only one TCR, exhibited a blunted hypertensive response to angiotensin II. Adoptive transfer of pan-T cells and CD8+ T cells but not CD4+/CD25? cells conferred hypertension to RAG-1?/? mice. In contrast, transfer of CD4+/CD25+ cells to wild type mice receiving angiotensin II decreased blood pressure. Mice treated with angiotensin II exhibited increased numbers of kidney CD4+ and CD8+ T cells. In response to a sodium/volume challenge, wild type and CD4?/? mice infused with angiotensin II retained water and sodium whereas CD8?/? mice did not. CD8?/? mice were also protected against angiotensin-induced endothelial dysfunction and vascular remodeling in the kidney. These data suggest that in the development of hypertension, an oligoclonal population of CD8+ cells accumulate in the kidney and likely contribute to hypertension by contributing to sodium and volume retention and vascular rarefaction. PMID:25259750

  10. Cerebral angiography, blood flow and vascular reactivity in progressive hypertension

    E-print Network

    Duong, Timothy Q.

    Cerebral angiography, blood flow and vascular reactivity in progressive hypertension Yunxia Li a Hypercapnia Spontaneous hypertensive rat Wistar Kyoto rats Chronic hypertension alters cerebral vascular to hypercapnia of multiple brain regions using arterial-spin-labeling technique in spontaneously hypertensive

  11. Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence?

    PubMed Central

    2014-01-01

    Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP). The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide) and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (pre)hypertension, stress-induced hypertension, and selected pharmacological and diet-induced models. PMID:24738065

  12. [Vascular aging, arterial hypertension and physical activity].

    PubMed

    Schmidt-Trucksäss, A; Weisser, B

    2011-11-01

    The present review delineates the significance of intima-media-thickness, arterial stiffness and endothelial function for vascular aging. There is profound evidence for an increase in intima-media-thickness and vascular stiffness not only during healthy aging but induced also by cardiovascular risk factors. There is a central role of arterial hypertension for this progression in both structural factors. In addition, both parameters are strongly associated with cardiovascular risk. Endothelial function measured as postischemic flow-mediated vasodilatation is a functional parameter which is decreased both in healthy aging and by cardiovascular risk factors. Physical activity modifies the influence of aging and risk factors on endothelial function. A positive influence of endurance exercise on vascular stiffness and endothelial function has been demonstrated in numerous studies. In long-term studies, regular physical activity has been shown to reduce the progression of intima-media-thickness. Thus, arterial hypertension accelerates vascular aging, while physical activity has a positive influence on a variety of vascular parameters associated with vascular aging. PMID:22068448

  13. Obligatory Role for B Cells in the Development of Angiotensin II-Dependent Hypertension.

    PubMed

    Chan, Christopher T; Sobey, Christopher G; Lieu, Maggie; Ferens, Dorota; Kett, Michelle M; Diep, Henry; Kim, Hyun Ah; Krishnan, Shalini M; Lewis, Caitlin V; Salimova, Ekaterina; Tipping, Peter; Vinh, Antony; Samuel, Chrishan S; Peter, Karlheinz; Guzik, Tomasz J; Kyaw, Tin S; Toh, Ban-Hock; Bobik, Alexander; Drummond, Grant R

    2015-11-01

    Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25% increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80% increase in splenic plasma cell numbers, (3) a 500% increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R(-/-)) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R(-/-) (?30±4 mm Hg) relative to wild-type (?41±5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R(-/-) mice displayed reduced IgG accumulation in the aorta, which was associated with 80% fewer aortic macrophages and a 70% reduction in transforming growth factor-? expression. BAFF-R(-/-) mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II-induced hypertension by ?35%. Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension. PMID:26351030

  14. Who Is at Risk for Pulmonary Hypertension?

    MedlinePLUS

    ... exact number of people who have pulmonary hypertension (PH) isn't known. Group 1 pulmonary arterial hypertension ( ... have group 1 PAH tend to be overweight . PH that occurs with another disease or condition is ...

  15. Hypertension—Listen to Your Heart

    MedlinePLUS

    Skip Navigation Bar Home Current Issue Past Issues Hypertension —Listen to Your Heart Past Issues / Summer 2006 ... G. Nabel Why should Americans be concerned about high blood pressure? Hypertension—or high blood pressure—is a serious ...

  16. [Benign intracranial hypo- and hypertension].

    PubMed

    Delvaux, V; Dioh, A; Schoenen, J

    1999-08-01

    Chronic headaches due to intracranial hypo- or hypertension (IHS codes 7.2 and 7.1) may be difficult to diagnose. In this article, we review their principal clinical characteristics, etiologies and therapies. Intracranial hypotension may be caused by CSF linkage, e.g. after lumbar puncture. It may also be "idiopathic" in which case a CSF leak, usually at the spinal level, may be difficult to demonstrate. Postural headache is the clinical hallmark of intracranial hypotension. The diagnosis is confirmed by leptomeningeal enhancement on MRI scans. The headache of benign intracranial hypertension may be aggravated by the supine position and accompanied by transient visual obscurations and tinnitus. Papillary edema supports the diagnosis but may be absent in some cases. Increased opening pressure of the CSF will confirm the diagnosis. Etiologies such as cerebral venous thrombosis, have to be excluded by adequate imaging methods. In both hypo- and hypertension syndromes, various therapeutic strategies have been proposed. PMID:10548894

  17. Prostacyclins in pulmonary hypertension treatment.

    PubMed

    Pereszlenyi, A; Harustiak, S; Klepetko, W

    2002-01-01

    Pulmonary hypertension is a rare, treacherous disease affecting the lungs and heart. Elevated pulmonary artery pressure (above 2.67 kPa) and pathologically high pulmonary vascular resistance are characteristic for this disease. This disease is insidiously progressive and often leads to sudden death mainly in middle and younger middle ages. Exhausting the traditional conservative means of treatment, lung/heart-lung transplantation offers the only possibility to improve the quality of patient's life. Nowadays more and more reports about the successful application of intravenous prostacyclin for treatment of this disease appear in specialized literature. Epoprostenol (prostacyclin PGI2) represents a new, potent drug for the treatment of pulmonary hypertension. The objective of this paper is to introduce prostacyclin PGI2 to experts and demonstrate new possibilities, procedures, trends in treatment of pulmonary hypertension. (Tab. 1, Ref. 30.). PMID:12413209

  18. Memories that last in hypertension.

    PubMed

    Itani, Hana A; Harrison, David G

    2015-06-01

    In recent years, it has become clear that the immune system contributes to the genesis of hypertension. Hypertensive stimuli, such as angiotensin II, DOCA-salt, and norepinephrine, cause T cells and monocytes/macrophages to accumulate in the kidney and vasculature. These cells release inflammatory cytokines, such as IL-6, interferon-?, and IL-17, that promote renal and vascular dysfunction. These cytokines also promote angiotensinogen production in the proximal tubule and Na(+) retention in the distal nephron and contribute to renal fibrosis and glomerular damage. For several years, we have observed accumulation of memory T cells in the kidney and vasculature. Given the propensity for memory cells to produce cytokines such as interferon-? and IL-17, interventions to prevent the formation or renal accumulation of specific memory T cell subsets could prevent end-organ damage and blood pressure elevation in response to hypertensive stimuli. PMID:25834073

  19. [HELLP syndrome in the postpartum period].

    PubMed

    Krzemie?-Wiczy?ska, Swiet?ana; Mikaszewska-Sokolewicz, Ma?gorzata; Bablok, Leszek; Mayzner-Zawadzka, Ewa

    2005-05-01

    The HELLP syndrome was described by Weinstein as a complication of pregnancy induced hypertension (PIH). There are few clinical reports about HELLP during postpartum period. We present the history of 31 years old pregnant patient, who developed in 36 week of her first pregnancy PIH, pregnancy was terminated in 39 week by cesarean section and postpartum period was complicated with HELLP syndrome (class I). The patient was treated surgically (hysterectomy), than continue at ICU. The treatment was successful without any late organ complications. PMID:16145859

  20. Renovascular hypertension: Pathophysiology, diagnosis, and treatment

    SciTech Connect

    Glorioso, N.; Laragh, J.H.; Rappelli, A.

    1987-01-01

    This book contains 42 selections. Some of the titles are: Clinical Pharmacology of Two Synthetic Atrial Natriuretics Peptides; Reflex Control of Renin Release in Normotensive and Hypertensive Humans; Renal Blood flow in Renovascular Hypertension; and Radioisotopic Studies in Renovascular Hypertension Before and After Surgery or Percutaneous Transluminal Renal Angioplasty.

  1. American Journal of Hypertension 1 Original article

    E-print Network

    Zabulis, Xenophon

    American Journal of Hypertension 1 Original article Assessment of microcirculation in the arterial disease. The predictive value of mild hypertensive retinopathy in terms of cardiovascular mortality and morbidity has not only been demonstrated in a recent multitudinal study among hypertensive and normotensive

  2. American Journal of Hypertension 1 Original article

    E-print Network

    Zabulis, Xenophon

    American Journal of Hypertension 1 Original article Divergent Retinal Vascular Abnormalities in Normotensive Persons and Patients With Never-Treated, Masked, White Coat Hypertension Areti Triantafyllou,1 Haidich,4 Chrysanthos Zamboulis1 and Stella Douma1 Background Hypertensive patients with retinal

  3. 20-HETE: A NEW TARGET FOR THE TREATMENT OF HYPERTENSION

    PubMed Central

    Williams, Jan M.; Murphy, Sydney; Burke, Marilyn; Roman, Richard J.

    2010-01-01

    Arachidonic acid (AA) is metabolized by enzymes of the CYP4A and 4F families to 20-hydroxyeicosatetraeonic acid (20-HETE) which plays an important role in the regulation of renal function, vascular tone and the long term control of arterial pressure. In the vasculature, 20-HETE is a potent vasoconstrictor and upregulation of the production of this compound contributes to the elevation in oxidative stress, endothelial dysfunction and the increase in peripheral vascular resistance associated with some forms of hypertension. In kidney, 20-HETE inhibits Na+ transport in the proximal tubule and thick ascending loop of Henle and deficiencies in the renal formation of 20-HETE contributes to sodium retention and the development of some salt-sensitive forms of hypertension. 20-HETE also has renoprotective actions and opposes the effects of transforming growth factor (TGF-?) to promote proteinuria and renal end organ damage in hypertension. Several new inhibitors of the synthesis of 20-HETE and 20-HETE agonists and antagonists have recently been developed. These compounds along with PPAR-? agonists that induce the renal formation 20-HETE appear to have promise as antihypertensive agents. This review summarizes the rationale for the development of drugs that target the 20-HETE pathway for the treatment of hypertension and associated cardiovascular complications. PMID:20930591

  4. Haemodynamic effects of chronic tetrandrine treatment in portal hypertensive rats.

    PubMed

    Huang, Y T; Cheng, Y R; Lin, H C; Chen, C F; Hong, C Y

    1997-08-01

    Tetrandrine is a calcium channel antagonist with reported antihypertensive effect. However, the potential role of tetrandrine as a therapeutic agent in portal hypertension has yet to be explored. The present study aimed to investigate the haemodynamic effects of chronic tetrandrine treatment on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Animals were allocated into one of two groups: a tetrandrine group and a vehicle group. Tetrandrine (20 mg/kg) or vehicle was administered by gavage every 12 h for 8 consecutive days, starting 1 day before ligation and continuing thereafter. After 8 days of tetrandrine treatment, systemic haemodynamics, organ blood flow and the degree of portal-systemic shunting were measured after an overnight fast. The portal venous pressure and protal tributary blood flow were significantly decreased, while portal territory as well as hepto-collateral vascular resistance significantly increased in the tetrandrine group compared with the vehicle group. The cardiac index was increased, while systemic vascular resistance was decreased, the the tetrandrine group. Mean arterial pressure, heart rate, portal-systemic shunting and bodyweight were similar between the two groups. Renal blood flow was decreased in the tetrandrine group. In conclusion, long-term treatment of tetrandrine reduced portal venous pressure and alleviated splanchnic hyperaemina in portal hypertensive rats without affecting the portal-systemic shunting. PMID:9304511

  5. Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

    MedlinePLUS

    ... field defects. These defects can occur in the central as well as the peripheral vision. Loss of color vision. What causes idiopathic intracranial hypertension? The cause is usually not known. A common explanation for increased pressure is a problem with the reabsorption of this ...

  6. Idiopathic intracranial hypertension without papilledema.

    PubMed

    Marcelis, J; Silberstein, S D

    1991-04-01

    We describe 10 patients with idiopathic intracranial hypertension who did not have papilledema. Idiopathic intracranial hypertension without papilledema, although rarely reported, may well be a clinically important headache syndrome. Historical and demographic features of patients with idiopathic intracranial hypertension without papilledema are similar to those of patients with papilledema. Obese women with chronic daily headache and symptoms of increased intracranial pressure, pulsatile tinnitus, history of head trauma or meningitis, an empty sella on imaging studies, or a headache that is unrelieved by standard therapy should have a diagnostic lumbar puncture. Findings from laboratory and neurologic investigations are normal in most patients with idiopathic intracranial hypertension without papilledema. Initial management should include removal of possible inciting agents, weight loss if applicable, and standard headache therapy. Lumbar puncture and diuretic therapy should precede a trial of corticosteroids. Surgery (lumboperitoneal or ventriculoperitoneal shunt or perhaps optic nerve sheath fenestration) may be indicated for prolonged incapacitating headache that is not responsive to medical management or lumbar puncture. PMID:2012512

  7. Hypertension control in brazilian publications

    PubMed Central

    Pinho, Natália de Alencar; Pierin, Angela Maria Geraldo

    2013-01-01

    Hypertension is a major public health problem due to its high prevalence and cardiovascular complications. Its treatment is aimed at reducing cardiovascular morbidity and mortality, its goal being to maintain blood pressure levels below 140/90 mm Hg. Hypertension control in Brazil is low, and nationwide rates are unknown. The objective of this review was to provide an overview on hypertension control in Brazil from publications in a database. We identified 45 publications. In population-based studies, the highest control rate (57.6%) was reported in a multicenter study in 100 municipalities and the city of São José do Rio Preto, São Paulo state (52.4%), while the lowest rates (around 10%) were identified in microregions of the Rio Grande do Sul state and in the city of Tubarão, Santa Catarina state. In conclusion, the studies assessed showed a wide variation in hypertension control rates. It is worth noting that the comparison between studies was a major limiting factor, because of the different methods used. PMID:24061761

  8. Hypertension screening in general practice

    PubMed Central

    Mayhew, S. R.

    1983-01-01

    In 1974 eight general practitioners decided to co-operate in a hypertension screening exercise in their practices. The reasons for the survey and the methodology are described and the results of screening over 28,000 patients are given. The cut-off point for normal diastolic blood pressure was 89 mmHg and 23,979 (85 per cent) patients were considered to be normosensitive on this criterion, 694 (2.5 per cent) patients were already known by their doctors to have hypertension; 991 (3.5 per cent) had an initial abnormal reading but subsequent readings were normal. The survey identified 2,018 patients (7.12 per cent) as being hypertensive and 575 (2 per cent) failed to complete the survey. Because of the ever-changing population in the practices, 100 per cent surveillance was not achieved. It is considered necessary to carry out continuous case finding for the presence of hypertensive patients in general practice. ImagesFigure 1.Figure 2. PMID:6887113

  9. Management of Hypertension in Obstructive Sleep Apnea.

    PubMed

    Furlan, Sofia F; Braz, Caio V; Lorenzi-Filho, Geraldo; Drager, Luciano F

    2015-12-01

    Obstructive sleep apnea (OSA) is considered to be a secondary form of hypertension and in clinical practice OSA is frequently associated with hypertension, even if proof of causality cannot be established. Growing evidence suggests that OSA is associated with worse blood pressure control, alterations in night-time blood pressure dipping, increased target organ damage, and arterial stiffness in patients with hypertension. This review summarizes the current evidence for managing hypertension in patients with OSA. Particular focus will be devoted to discuss the impact of lifestyle changes, preferences for anti-hypertensive treatment in patients with OSA, and the effects of OSA treatment with continuous positive airway pressure on blood pressure. PMID:26482751

  10. Misconceptions and facts about treating hypertension.

    PubMed

    Argulian, Edgar; Grossman, Ehud; Messerli, Franz H

    2015-05-01

    Hypertension is a powerful risk factor strongly linked to adverse cardiovascular outcomes. Because of its high prevalence, health care providers at many levels are involved in treating hypertension. Distinct progress has been made in improving the rates of hypertension awareness and treatment over years, but the overall control of hypertension remains inadequate. Several recent guidelines from different sources have been put forward in an attempt to bridge the gap between existing evidence and clinical practice. Despite this effort, several misconceptions about treating hypertensive cardiovascular disease continue to persist among clinicians. This review highlights some of the misconceptions regarding antihypertensive therapy. PMID:25486449

  11. Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension.

    PubMed

    Li, Hong-Bao; Qin, Da-Nian; Ma, Le; Miao, Yu-Wang; Zhang, Dong-Mei; Lu, Yan; Song, Xin-Ai; Zhu, Guo-Qing; Kang, Yu-Ming

    2014-09-01

    The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10?g/h) or vehicle via osmotic minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. PMID:24937322

  12. Effect of Huanglian Jiedu Decoction on Thoracic Aorta Gene Expression in Spontaneous Hypertensive Rats

    PubMed Central

    Yue, Gui-Hua; Zhuo, Shao-Yuan; Zhang, Zhuo; Gao, Yi-Wen; Luo, Yuan

    2014-01-01

    Objective. Hypertension is one of the most common cardiovascular disorders with high mortality. Here we explored the antihypertension effects of Huanglian Jiedu Decoction (HJD) on thoracic aorta gene expression in spontaneous hypertensive rats. Methods. A rat model of spontaneous hypertension was used. The gene change profile of thoracic aorta after JHD treatment was assessed by GeneChip(GC) analysis using the Agilent Whole Rat Genome Oligo Microarray. Results. Hypertension induced 441 genes upregulated and 417 genes downregulated compared with the normal control group. Treatment of HJD resulted in 76 genes downregulated and 20 genes upregulated. GC data analysis showed that the majority of change genes were involved in immune system process, developmental process, and cell death. Conclusion. Hypertension altered expression of many genes that regulate various biological functions. HJD significantly reduced hypertension and altered the gene expression profiles of SHR rats. These changing genes were involved in many cellular functions such as regulating smooth muscle contraction, Ca(2+) homeostasis, and NO pathway. This study provides the potential novel insights into hypertension and antihypertension effects of HJD. PMID:24744811

  13. Angiotensin-converting enzyme gene polymorphisms and hypertension in occupational noise exposure in Egypt

    PubMed Central

    Zawilla, Nermin; Shaker, Dalia; Abdelaal, Amaal; Aref, Wael

    2014-01-01

    Background: The gene–environment interaction in the pathogenesis of hypertension has not been extensively studied in occupational noise. Objectives: The aim of this study was to determine the relationship between noise and hypertension in Egyptian workers, the interaction of angiotensin-converting enzyme (ACE) gene polymorphisms as modifiers, and the possible relationship between noise hearing impairment and hypertension. Methods: Study subjects were divided into two groups depending on noise exposure level. The control group (n?=?161) was exposed to noise intensity <85 dB and the exposed group (n?=?217) was exposed to noise intensity ?85 dB. A polymerase chain reaction was used to differentiate the various genotypes of ACE insertion/deletion (I/D) and ACE G2350A. Results: Noise significantly increased the likelihood of hypertension. Carriers of the genotypes AG, GG, and DD were vulnerable to hypertension on noise exposure. No association between hypertension and hearing impairment or noise-induced hearing loss (NIHL) was found. Conclusion: Our results support the association between ACE gene polymorphisms and occurrence of hypertension in noise-exposed workers. PMID:25000107

  14. Magnetic Resonance Imaging in Pediatric Pulmonary Hypertension

    PubMed Central

    Olgunturk, Rana; Cevik, Ayhan; Terlemez, Semiha; Kacar, Emre; Oner, Yusuf Ali

    2015-01-01

    The present study aims to determine the efficacy and reliability of cardiovascular magnetic resonance imaging in establishing the diagnosis and prognosis of pulmonary hypertension in children. This is a retrospective comparison of 25 children with pulmonary hypertension and a control group comprising 19 healthy children. The diagnosis of pulmonary hypertension was made when the mean pulmonary artery pressure was ?25 mmHg by catheter angiography. The children with pulmonary hypertension had significantly lower body mass indices than did the healthy children (P=0.048). In addition, the children with pulmonary hypertension had significantly larger main pulmonary artery diameters and ascending aortic diameters (both P=0.001) but statistically similar ratios of main pulmonary artery diameter-to-ascending aortic diameter. If the main pulmonary artery diameter was ?25 mm, pediatric pulmonary hypertension was diagnosed with 72% sensitivity and 84% specificity. In the event that the ratio of main pulmonary artery diameter-to-ascending aorta diameter was ?1, pediatric pulmonary hypertension was diagnosed with 60% sensitivity and 53% specificity. When compared with children who had New York Heart Association functional class II pulmonary hypertension, the children with functional class III pulmonary hypertension had significantly larger main (P=0.046), right (P=0.036), and left (P=0.003) pulmonary arteries. Cardiovascular magnetic resonance imaging is useful in the diagnosis of children with pulmonary hypertension. Pediatric pulmonary hypertension can be diagnosed with high sensitivity and specificity when the main pulmonary artery diameter measures ?25 mm. PMID:26175631

  15. DECREASED HEART RATE IS ASSOCIATED WITH CARBAMATE-INDUCED ACTIVATION OF PRO-INFLAMMATORY SERUM PROTEINS.

    EPA Science Inventory

    Previously we reported that chlorpyrifos (CHP), an irreversible cholinesterase (ChE) inhibitor, induces hypertension in rats. Concomitant with hypertension, we found an increase in C-reactive protein, macrophage inflammatory protein-2 , monocyte chemotactic protein-5 and interfer...

  16. The treatment of hypertension in obese patients.

    PubMed

    Wofford, Marion R; Smith, Grant; Minor, Deborah S

    2008-04-01

    Hypertension causes a significant disease burden in all racial and ethnic groups and is directly attributable to excess weight in most cases. The relationship between increasing body mass index and hypertension prevalence has been recognized for decades. Epidemiologic studies clearly demonstrate the correlation between body weight and blood pressure in obese and lean populations. Most patients with hypertension are overweight or obese, and loss of excess weight lowers blood pressure. Although the epidemiologic relationship is clear, the understanding of mechanisms linking hypertension and weight gain is still evolving. Lifestyle modifications and specific pharmacologic agents address many of the known mechanisms; however, blood pressure remains difficult to control in obese hypertensive patients. This review highlights the association of obesity and hypertension, identifies potential mechanisms for this association, and describes nonpharmacologic and pharmacologic strategies that offer potential benefits for the obese patient with hypertension. PMID:18474182

  17. Impedance Cardiographic (ICG) Assessment of Pregnant Women With Severe Hypertension to Assess Impact of Standard Therapy

    ClinicalTrials.gov

    2013-12-11

    Pregnancy; Proteinuria, With Hypertension (Severe Pre-eclampsia); Delivery; Proteinuria, With Gestational Hypertension (Pre-eclampsia, Severe); Pregnancy; Hypertension, Gestational Hypertension, With Albuminuria (Severe Pre-eclampsia)

  18. Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells

    PubMed Central

    Su, Jie; Xu, Han-Ting; Yu, Jing-Jing; Gao, Jian-Li; Lei, Jing; Yin, Qiao-Shan; Li, Bo; Pang, Min-Xia; Su, Min-Xia; Mi, Wen-Jia; Chen, Su-Hong; Lv, Gui-Yuan

    2015-01-01

    Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs) and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo. Luteolin could inhibit angiotensin II- (Ang II-) induced proliferation and migration of vascular smooth muscle cells (VSMCs). Dichlorofluorescein diacetate (DCFH-DA) staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA) protein level. Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS. PMID:26495010

  19. Calcitonin Gene-Related Peptide (CGRP) Receptors Are Important to Maintain Cerebrovascular Reactivity in Chronic Hypertension

    PubMed Central

    Wang, Zhenghui; Martorell, Belén Cantó; Wälchli, Thomas; Vogel, Olga; Fischer, Jan; Born, Walter; Vogel, Johannes

    2015-01-01

    Cerebral blood flow autoregulation (CA) shifts to higher blood pressures in chronic hypertensive patients, which increases their risk for brain damage. Although cerebral vascular smooth muscle cells express the potent vasodilatatory peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) and their receptors (calcitonin receptor-like receptor (Calclr), receptor-modifying proteins (RAMP) 1 and 2), their contribution to CA during chronic hypertension is poorly understood. Here we report that chronic (10 weeks) hypertensive (one-kidney-one-clip-method) mice overexpressing the Calclr in smooth muscle cells (CLR-tg), which increases the natural sensitivity of the brain vasculature to CGRP and AM show significantly better blood pressure drop-induced cerebrovascular reactivity than wt controls. Compared to sham mice, this was paralleled by increased cerebral CGRP-binding sites (receptor autoradiography), significantly in CLR-tg but not wt mice. AM-binding sites remained unchanged. Whereas hypertension did not alter RAMP-1 expression (droplet digital (dd) PCR) in either mouse line, RAMP-2 expression dropped significantly in both mouse lines by about 65%. Moreover, in wt only Calclr expression was reduced by about 70% parallel to an increase of smooth muscle actin (Acta2) expression. Thus, chronic hypertension induces a stoichiometric shift between CGRP and AM receptors in favor of the CGRP receptor. However, the parallel reduction of Calclr expression observed in wt mice but not CLR-tg mice appears to be a key mechanism in chronic hypertension impairing cerebrovascular reactivity. PMID:25860809

  20. Increased angiogenesis in portal hypertensive rats: role of nitric oxide.

    PubMed

    Sumanovski, L T; Battegay, E; Stumm, M; van der Kooij, M; Sieber, C C

    1999-04-01

    Systemic and especially splanchnic arterial vasodilation accompany chronic portal hypertension. Different soluble mediators causing this vasodilation have been proposed, the strongest evidence being for nitric oxide (NO). No data exist if structural vascular changes may partly account for this vasodilatory state. Here, we developed a new in vivo quantitative angiogenesis assay in the abdominal cavity and determined if: 1) portal hypertensive rats show increased angiogenesis; and 2) angiogenesis is altered by inhibiting NO formation. Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls (CON). During the index operation (day 0), a teflon ring filled with collagen I (Vitrogen 100) was sutured in the mesenteric cavity. After 16 days, rings were explanted, embedded in paraffin, and ingrown vessels counted using a morphometry system. The role of NO was tested by adding an antagonist of NO formation (Nomega-nitro-L-arginine [NNA], 3.3 mg/kg/d) into the drinking water. The mean number of ingrown vessels per implant was significantly higher in PVL rats compared with CON rats, i.e., 1,453 +/- 187 versus 888 +/- 116, respectively (P <.05; N = 5 per group). NNA significantly (P <.01) inhibited angiogenesis in PVL (202 +/- 124; N = 5) and in CON (174 +/- 25; N = 6) rats, respectively. In contrast, the beta-adrenergic blocker, propranolol, did not prevent angiogenesis either in PVL or CON rats in a separate set of experiments (data not shown). The conclusions drawn from this study are that: 1) rats with portal hypertension show increased angiogenesis; and 2) inhibition of NO formation significantly prevents angiogenesis in both PVL and CON rats. Therefore, splanchnic vasodilation in chronic portal hypertension may also be a result of structural changes. PMID:10094944

  1. Cardiac transcriptome analysis in obesity-related hypertension.

    PubMed

    Philip-Couderc, Pierre; Smih, Fatima; Pelat, Michel; Vidal, Cyril; Verwaerde, Patrick; Pathak, Atul; Buys, Sophie; Galinier, Michel; Senard, Jean-Michel; Rouet, Philippe

    2003-03-01

    Obesity is associated with volumetric arterial hypertension and with early increase in heart rate and decreased heart rate variability. The consequences of obesity-related hypertension on heart gene regulation are poorly known and were investigated in a model of obesity-related hypertension induced by high fat diet in dogs. When compared with control animals (n=6), a 9-week high fat diet (n=6) provoked significant weight gain and increased blood pressure load and heart rate but failed to significantly change left ventricular mass assessed by echocardiography. Subtractive hybridization of dog heart cDNA libraries were used to generate sublibraries containing differentially expressed cDNAs that were in turn spotted onto membranes to create custom microarrays. Hybridizations of these microarrays with complex probes representing mRNAs expressed in right atria and left ventricles from obese hypertensive and control dogs were performed. Thirty-eight differentially expressed genes were identified; altered expression was confirmed by Northern blot analysis in 15. In addition, real-time quantitative polymerase chain reaction confirmed differential expression for 80% of the randomly chosen tested genes. Once identified, transcripts were categorized into groups involved in metabolism, cell signaling, ionic regulation, cell proliferation, protein synthesis, and tissue remodeling. In addition, we found a set of 11 cDNAs encoding proteins with unknown functions. This study clearly shows that obesity-related hypertension, lasting for only 9 weeks, causes marked changes in gene expression in right atrium as well as the left ventricle that may contribute to early functional changes in heart function and to long-term structural changes such as left ventricular hypertrophy and remodeling. PMID:12623937

  2. Potential renovascular hypertension, space missions, and the role of magnesium.

    PubMed

    Rowe, William J

    2009-01-01

    Space flight (SF) and dust inhalation in habitats cause hypertension whereas in SF (alone) there is no consistent hypertension but reduced diurnal blood pressure (BP) variation instead. Current pharmaceutical subcutaneous delivery systems are inadequate and there is impairment in the absorption, metabolism, excretion, and deterioration of some pharmaceuticals. Data obtained from the National Aeronautics and Space Administration through the Freedom of Information Act shows that Irwin returned from his 12-day Apollo 15 mission in 1971 and was administered a bicycle stress test. With just three minutes of exercise, his BP was >275/125 mm Hg (heart rate of only 130 beats per minute). There was no acute renal insult. Irwin's apparent spontaneous remission is suggested to be related to the increase of a protective vasodilator, and his atrial natriuretic peptide (ANP) reduced with SF because of reduced plasma volume. With invariable malabsorption and loss of bone/muscle storage sites, there are significant (P < 0.0001) reductions of magnesium (Mg) required for ANP synthesis and release. Reductions of Mg and ANP can trigger pronounced angiotensin (200%), endothelin, and catecholamine elevations (clearly shown in recent years) and vicious cycles between the latter and Mg deficits. There is proteinuria, elevated creatinine, and reduced renal concentrating ability with the potential for progressive inflammatory and oxidative stress-induced renal disease and hypertension with vicious cycles. After SF, animals show myocardial endothelial injuries and increased vascular resistance of extremities in humans. Even without dust, hypertension might eventually develop from renovascular hypertension during very long missions. Without sufficient endothelial protection from pharmaceuticals, a comprehensive gene research program should begin now. PMID:21694921

  3. [Serotonin and hypertension in preeclampsia-eclampsia syndrome].

    PubMed

    Ghisoni, L

    1990-01-01

    The preeclampsia-eclampsia syndrome is a severe complication of the third trimester of pregnancy and represents the first cause of maternal death. It is mainly characterized by: weight increase, proteinuria and hypertension and can evolve with convulsions and maternal death. The etiology still remains unknown although a series of events have been identified, starting with endothelial damage and local vasoconstriction leading to hypertension. These events occur at first locally in the placental district and become generalized. This paper reports experimental and clinical data in order to demonstrate: 1) the presence of a substance that could evoke experimentally the damage present in this syndrome, 2) a mechanism that delivers such a substance to its primary action site, the placenta, and 3) the possibility to inhibit either the substance or the delivery mechanism in order to prevent this disease. Serotonin appears to play an important role in the chain of events leading to preeclampsia. Certain histological aspects, present in pregnant women with this type of hypertension, have been observed in experimental animals after the administration of serotonin. Platelet derived serotonin could be sufficient, in the case of endothelial damage, to determine vasospasm. In a condition of hypercoagulability, such as pregnancy, this situation can trigger a chain of mechanisms ending with renal damage. Low dose aspirin seems a valid therapeutic approach reducing thromboxane concentrations and therefore preventing vasospasm. In this way the pathogenetic sequence culminating in the preeclampsia-eclampsia syndrome is interrupted. Ketanserin inhibits the hypertensive potential of serotonin by selectively acting on S2 serotonin receptors and appears to be an effective treatment in this type of pregnancy induced hypertension. PMID:2102137

  4. Hypertension Vaccine may be a boon to millions in developing world

    PubMed Central

    Bairwa, Mohan; Pilania, Manju; Gupta, Vivek; Yadav, Kapil

    2014-01-01

    Hypertension affects around 40% adults aged 25 years and more worldwide, and accounts for 7% of total disability-adjusted life-years. A simple algorithmic program is required to manage hypertension consisting of screening, life style measures, treatment and follow-up, a reliable drug supply and distribution system, and a credible health information system. Despite availability of effective antihypertensive drugs, long term treatment is still costly, tedious, and at the population level rather unsuccessful. Hypertension leaves patients and families with an avoidable heavy economic burden due to failure to control blood pressure. Health policy needs to address gross imbalance between prevention and management by increasing contribution to the preventive programs. During 21st century, the risk factors for morbidity and mortality have been changed, and researchers have started to work upon vaccines against lifestyle diseases like hypertension, diabetes etc. Researchers began experimenting with vaccines against the renin-angiotensin system to control hypertension around six decades ago. The vaccine candidates against hypertension namely ATR12181, pHAV-4Ang IIs, CYT006-AngQb, AngI-R, ATRQ?-001 have shown promising results. A candidate vaccine, CYT006-AngQb, has crossed initial phase and moved into phase 2 trials. However, more human studies in subsequent phases of trials are required to establish the safety and efficacy of anti-hypertensive vaccine. If proved safe and cost effective, a vaccine even with 50% efficacy against hypertension may protect about 90 million people from hypertension and its heavy economic burden. It can be an appropriate solution for low compliance to antihypertensive drug therapy as well as an avalanche to induce efforts on various chronic disease vaccine development programs. PMID:24365998

  5. Brain ACE2 overexpression reduces DOCA-salt hypertension independently of endoplasmic reticulum stress.

    PubMed

    Xia, Huijing; de Queiroz, Thyago Moreira; Sriramula, Srinivas; Feng, Yumei; Johnson, Tanya; Mungrue, Imran N; Lazartigues, Eric

    2015-03-01

    Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension. SL and nontransgenic (NT) mice underwent DOCA-salt or sham treatment while infected with an adenoassociated virus (AAV) encoding Cre recombinase (AAV-Cre) or a control virus (AAV-green fluorescent protein) to the SFO or PVN. DOCA-salt-induced hypertension was reduced in SL mice, with hACE2 overexpression in the brain. This reduction was only partially blunted by knockdown of hACE2 in the SFO or PVN, suggesting that both regions are involved but not essential for ACE2 regulation of blood pressure (BP). DOCA-salt treatment did not increase the protein levels of ER stress and autophagy markers in NT mice, despite a significant increase in BP. In addition, these markers were not affected by hACE2 overexpression in the brain, despite a significant reduction of hypertension in SL mice. To further assess the role of ER stress in neurogenic hypertension, NT mice were infused intracerebroventricularlly with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, during DOCA-salt treatment. However, TUDCA infusion failed to blunt the development of hypertension in NT mice. Our data suggest that brain ER stress does not contribute to DOCA-salt hypertension and that ACE2 blunts neurogenic hypertension independently of ER stress. PMID:25519733

  6. Digoxin inhibits development of hypoxic pulmonary hypertension in mice.

    PubMed

    Abud, Edsel M; Maylor, Julie; Undem, Clark; Punjabi, Arjun; Zaiman, Ari L; Myers, Allen C; Sylvester, J T; Semenza, Gregg L; Shimoda, Larissa A

    2012-01-24

    Chronic hypoxia is an inciting factor for the development of pulmonary arterial hypertension. The mechanisms involved in the development of hypoxic pulmonary hypertension (HPH) include hypoxia-inducible factor 1 (HIF-1)-dependent transactivation of genes controlling pulmonary arterial smooth muscle cell (PASMC) intracellular calcium concentration ([Ca(2+)](i)) and pH. Recently, digoxin was shown to inhibit HIF-1 transcriptional activity. In this study, we tested the hypothesis that digoxin could prevent and reverse the development of HPH. Mice were injected daily with saline or digoxin and exposed to room air or ambient hypoxia for 3 wk. Treatment with digoxin attenuated the development of right ventricle (RV) hypertrophy and prevented the pulmonary vascular remodeling and increases in PASMC [Ca(2+)](i), pH, and RV pressure that occur in mice exposed to chronic hypoxia. When started after pulmonary hypertension was established, digoxin attenuated the hypoxia-induced increases in RV pressure and PASMC pH and [Ca(2+)](i). These preclinical data support a role for HIF-1 inhibitors in the treatment of HPH. PMID:22232678

  7. DIASTOLIC DYSFUNCTION: A LINK BETWEEN HYPERTENSION AND HEART FAILURE

    PubMed Central

    Lalande, Sophie; Johnson, Bruce D.

    2009-01-01

    Summary Diastolic heart failure is characterized by the symptoms and signs of heart failure, a preserved ejection fraction and abnormal left ventricular (LV) diastolic function caused by a decreased LV compliance and relaxation. The signs and symptoms of diastolic heart failure are indistinguishable from those of heart failure related to systolic dysfunction; therefore, the diagnosis of diastolic heart failure is often one of exclusion. The majority of patients with heart failure and preserved ejection fraction have a history of hypertension. Hypertension induces a compensatory thickening of the ventricular wall in an attempt to normalize wall stress, which results in LV concentric hypertrophy, which in turn decreases LV compliance and LV diastolic filling. There is an abnormal accumulation of fibrillar collagen accompanying the hypertension-induced LV hypertrophy, which is also associated with decreased compliance and LV diastolic dysfunction. There are no specific guidelines for treating diastolic heart failure, but pharmacological treatment should be directed at normalizing blood pressure, promoting regression of LV hypertrophy, preventing tachycardia and treating symptoms of congestion. Preventive strategies directed toward an early and aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of diastolic heart failure. PMID:18806901

  8. Canadian efforts to prevent and control hypertension.

    PubMed

    Campbell, Norman R C; Chen, Guanmin

    2010-01-01

    Suboptimum blood pressure is estimated to be the leading risk factor for death worldwide and is associated with 13.5% of deaths globally. The clinical diagnosis of hypertension affects one in four adults globally and is expected to increase by 60% between 2000 and 2025. Clearly, global efforts to prevent and control hypertension are important health issues. While Canada had a prevalence of hypertension similar to that of the United States in the early 1990 s, the treatment and control rate was only 13% compared with 25% in the United States. A national strategic plan was developed, and a coalition of organizations and health care professional and scientist volunteers actively implemented parts of the strategy. Specific initiatives that have evolved include the development of hypertension knowledge translation programs for health professionals, the public and people with hypertension, an outcomes research program to assess the impact of hypertension and guide national-, regional- and community-based knowledge translation interventions, and a program to reduce the prevalence of hypertension by decreasing sodium additives in food. These initiatives have relied on the active involvement of health care professional volunteers, health care professional and scientific organizations and various government departments. There have been large increases in the diagnosis and treatment of hypertension, with corresponding reductions in cardiovascular disease and total mortality associated with the start of the hypertension initiatives. As a result, Canada is becoming recognized as a world leader in the prevention, treatment and control of hypertension. PMID:20847986

  9. Emergency Management of Hypertension in Children

    PubMed Central

    Singh, Dinesh; Akingbola, Olugbenga; Yosypiv, Ihor; El-Dahr, Samir

    2012-01-01

    Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH), particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information. PMID:22577545

  10. Status of lifestyle modifications in hypertension.

    PubMed

    Chhabra, M K; Lal, A; Sharma, K K

    2001-09-01

    Hypertension is essentially the elevation of arterial blood pressure beyond an arbitrary cut off point, though the dividing line between normal and elevated BP is lacking. Hypertension can be classified into primary, essential or idiopathic hypertension on one hand, and secondary one due to some disease itself. In treating hypertension, antihypertensives have their role, but attention may be directed towards some lifestyle modifications. As regarding dietary interventions, calorie restriction may influence the minimisation of BP. Body weight reduction, less alcohol consumption, salt restriction, potassium and calcium supplementation can enhance the process of lowering BP. The role of magnesium in hypertension is debatable. Serum cholesterol level is commonly elevated in hypertensive patients and its reduction reduces the risk of non-fatal coronary events. Diet rich in plant fibres either alone or with a low fat, low sodium could lower the BP by about 5 mm Hg in hypertensives. The omega-3-polyunsaturated fatty acids found in highest concentrations in cold water fishes have a modest antihypertensive effect. Caffeine contained in two cups of coffee may raise the BP by 5 mm Hg in infrequent users but in habitual users, caffeine has no role. Deficiency of vitamin C might lead to hypertension. As regarding behavioural changes, stopping smoking, regular physical exercise, relaxation therapies like yoga, etc, have definite beneficial effect on hypertensives. The antihypertensive effect of lifestyle modifications may obviate drug therapy. For this one or more of the lifestyle modifications should be tried initially in all hypertensive patients. PMID:12018559

  11. Reduction of transmural sup 125 I-albumin concentration in rat aortic media by chronic hypertension

    SciTech Connect

    Belmin, J.; Michel, J.B.; Curmi, P.A.; Salzmann, J.L.; Juan, L.; Tedgui, A. )

    1991-03-01

    Relative 125I-albumin concentration was measured in vivo in the aortic media of sham-operated (n = 10) and hypertensive (two-kidney, one clip) rats, untreated (n = 8) or treated (n = 10) by an angiotensin converting enzyme inhibitor (CEI, Trandolapril). Blood pressure was acutely lowered to a normal level at the time of the experiment in hypertensive rats (n = 7) to separate the direct effect of increased pressure from the effect of pressure-induced structural changes. Relative tissue concentration profiles of labeled albumin across the media were obtained using a serial frozen-sectioning technique. In hypertensive rats, the mean medial albumin concentration decreased by 35% in the ascending arch and 32% in the descending arch (p less than 0.01). When blood pressure was acutely lowered in hypertensive animals, this value decreased further by 56% in the ascending arch, 48% in the descending arch (p less than 0.01), and 22% in the thoracic aorta (p less than 0.05) as compared with controls. The medial thickness in hypertensive rats was significantly increased (more in the ascending arch than in the rest of the aorta). Four-week CEI treatment reversed hypertension and medial thickening, but the mean medial albumin concentration remained significantly lower in the arch (by 36% in the ascending part and 40% in the descending part, p less than 0.01). The collagen content in the thoracic aorta was significantly increased in hypertensive rats (by 40%, p less than 0.01) and remained increased (by 29%, p less than 0.01) after CEI treatment. These results suggested that the hypertension-induced structural changes might reduce the medial distribution volume for albumin, whereas elevated blood pressure per se tended to enhance albumin concentration within the media.

  12. Burden of Diabetes Related Complications Among Hypertensive and Non Hypertensive Diabetics: A Comparative Study

    PubMed Central

    Kesavamoorthy, Goutham; Singh, Awnish K; Sharma, Shruti; Kasav, Jyoti Bala; Joshi, Ashish

    2015-01-01

    Background Diabetes and hypertension are the conditions with overlapping risk factors and complications. Objective of present study was to compare the burden of complications of diabetes among hypertensive and non hypertensive diabetes individuals. Materials and Methods This cross-sectional study was conducted at Saveetha medical college and hospital, Chennai, India. A total of 100 diabetics having hypertension and 50 non-hypertensive diabetic patients were enrolled on the basis of purposive sampling. Information about sociodemograpic characteristics, general health, health distress, diabetes symptoms, communication with physician, healthcare utilization and lifetime occurrence of diabetes related complications. Mean, standard deviation and median of continuous variables and proportion of categorical variables were recorded. Results Average age of the hypertensive diabetes patients (M=57; SD=11) was higher than non hypertensive diabetes patients (M=52; SD=11) which was statistically significant (p=.009). Diabetic neuropathy was reported by 45% of the hypertensive and 38% of the non-hypertensive diabetics. Mean self reported general health score was higher among hypertensive diabetic participants (M=3.4; SD=1) in comparison to non hypertensive diabetic participants (M=3; SD=1) and it was found statistically significant (p=.03) indicating towards poor self health perception among hypertensive’s. Results of the study have shown that the proportion of participants who have prepared any list of questions before visiting doctor’s clinic (fairly often to always) was significantly higher among hypertensive diabetics (30%) in comparison to non-hypertensive diabetics (14%). Conclusion The proportion of participants reporting diabetes neuropathy and retinopathy was higher among hypertensive diabetics in comparison to non hypertensive diabetics. PMID:26500926

  13. Connecting tubule glomerular feedback (CTGF) in Hypertension

    PubMed Central

    Wang, Hong; D'Ambrosio, Martin A.; Garvin, Jeffrey L.; Ren, Yilin; Carretero, Oscar A.

    2013-01-01

    In Dahl salt-sensitive rats (Dahl SS), glomerular capillary pressure (PGC) increases in response to high salt intake and this is accompanied by significant glomerular injury compared to spontaneously hypertensive rats (SHR) with similar blood pressure. PGC is controlled mainly by afferent arteriolar (Af-Art) resistance, which is regulated by the vasoconstrictor tubuloglomerular feedback (TGF) and the vasodilator connecting tubule glomerular feedback (CTGF). We hypothesized that Dahl SS have a decreased TGF response and enhanced TGF resetting compared to SHR, and that these differences are due in part to an increase in CTGF. In vivo, using micropuncture we measured stop-flow pressure (PSF, a surrogate of PGC). TGF was calculated as the maximal decrease in PSF caused by increasing nephron perfusion, TGF resetting as the attenuation in TGF induced by high salt diet, and CTGF as the difference in TGF response before and during CTGF inhibition with benzamil. Compared to SHR, Dahl SS had 1) lower TGF responses in normal (6.6±0.1 vs. 11.0±0.2 mm Hg; P<0.001) and high-salt diets (3.3±0.1 vs. 10.1±0.3 mmHg; P<0.001), 2) greater TGF resetting (3.3±0.1 vs. 1.0±0.3 mmHg; P<0.001), and 3) greater CTGF (3.4±0.4 vs. 1.2±0.1 mmHg; P<0.001). We conclude that Dahl SS have lower TGF and greater CTGF than SHR, and that CTGF antagonizes TGF. Furthermore, CTGF is enhanced by a high-salt diet and contributes significantly to TGF resetting. Our findings may explain in part the increase in vasodilatation, PGC, and glomerular damage in salt-sensitive hypertension during high salt intake. PMID:23959547

  14. Effects of spontaneously hypertensive rat plasma on blood pressure and tail artery calcium uptake in normotensive rats

    SciTech Connect

    Lewanczuk, R.Z.; Wang, J.; Zhang, Z.R.; Pang, P.K.

    1989-01-01

    Previous studies have described the presence of humoral hypertensive factors in spontaneously hypertensive rats (SHR). Other studies have described factors that increase calcium uptake in vascular tissue. In this study, we attempted to confirm, and thereby correlate, the presence of both types of factors in SHR plasma. Intravenous infusion or bolus administration of dialyzed SHR plasma consistently induced an increase in blood pressure in normotensive rats. This hypertensive response was somewhat delayed, with peak blood pressures occurring /sup 45/ minutes after bolus administration and 90 minutes after infusion of SHR plasma. Spontaneously hypertensive rat plasma also increased /sup 45/Ca uptake in isolated normotensive rat tail arteries in a dose-dependent manner, with a time course similar to that for the hypertensive response to bolus administration. These findings suggest, therefore, that a substance exists in SHR plasma that can increase intracellular calcium in vascular tissues and thereby increase blood pressure.

  15. Inflammation and therapy for hypertension.

    PubMed

    Laffer, Cheryl L; Elijovich, Fernando

    2010-08-01

    It is currently accepted that hypertension, atherosclerosis, and diabetes are disorders with subtle or overt activation of inflammatory mediators. Therefore, it has become increasingly important to ascertain whether current antihypertensive drug families have proinflammatory or anti-inflammatory actions that modify the outcomes of their hemodynamic effects on blood pressure. We review the current state of knowledge about the effects of the major classes of available antihypertensive agents on inflammation and speculate on the possible contribution of these effects to observations in clinical trials. We suggest that a strategy of drug development specifically addressing inflammation in hypertension may provide increased benefit in terms of target organ damage, and we describe some examples of these promising developments. PMID:20524088

  16. Hypertension reduction through forgiveness training.

    PubMed

    Tibbits, Dick; Ellis, Greg; Piramelli, Chris; Luskin, Fred; Lukman, Roy

    2006-01-01

    The objective of this study was to determine if patients with diagnosed stage-1 hypertension could benefit by a forgiveness training program to achieve measurable reductions in anger expression and blood pressure. Twenty-five participants were randomly divided into wait-listed control and intervention groups. The control group monitored blood pressure while the intervention group participated in an 8-week forgiveness training program. At the end of eight weeks, the wait listed group became an intervention group. Those who received forgiveness training achieved significant reductions in anger expression when compared to the control group. While reductions in blood pressure were not achieved by all the participants, those participants who entered the program with elevated anger expression scores did achieve significant reductions in blood pressure. It is suggested that forgiveness training may be an effective clinical intervention for some hypertensive patients with elevated levels of anger. PMID:16733947

  17. [Management of juvenile ocular hypertension].

    PubMed

    Sun, Xing-huai

    2012-06-01

    Ocular hypertensions (OHTs) in juvenile are characterized by occurrence in teenage with intraocular pressure (IOP) frequently fluctuated and increased over 30 mm Hg (1 mm Hg = 0.133 kPa) without any ocular symptoms and disturbance of visual acuity. IOPs are normalized in the majorities of juvenile over adolescence stage with long-term follow up. The medical terminology of 'adolescence IOP fluctuation' or 'adolescence ocular hypertension' is therefore used. The diagnosis and management of juvenile OHT remain difficult clinical challenges. OHTs in juvenile sometimes are incorrectly diagnosed due to inappropriate IOP measurement and thicker central cornea as younger children are non-compliant and resisting the examination. In this paper, we reviewed OHT in juvenile in the light of significant studies in the past and based on our experience of clinical practice in order to provide a better understanding and management of OHTs in juvenile. PMID:22943799

  18. Epidemiology, pathophysiology, and treatment of hypertension in ischaemic stroke patients.

    PubMed

    Hisham, Nur Fatirul; Bayraktutan, Ulvi

    2013-10-01

    Stroke continues to be one of the leading causes of mortality and morbidity worldwide. There are 2 main types of stroke: ischaemic strokes, which are caused by obstruction of the blood vessels leading to or within the brain, and haemorrhagic strokes, which are induced by the disruption of blood vessels. Stroke is a disease of multifactorial aetiology that may develop as an end state in patients with serious vascular conditions--most notably, uncontrolled arterial hypertension--thereby necessitating the effective control of this risk factor to prevent stroke or its recurrence. This paper focuses specifically on the epidemiology and pathogenesis of ischaemic stroke mainly in chronically hypertensive patients and pays particular attention to the efficacy of a select group of routinely used major antihypertensive drugs (i.e., angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, and calcium channel blockers) in the treatment of strokes. PMID:22682972

  19. Compared myocardial and vascular effects of captopril and dihydralazine during hypertension development in spontaneously hypertensive rats.

    PubMed Central

    Freslon, J. L.; Giudicelli, J. F.

    1983-01-01

    When administered to young spontaneously hypertensive rats (SHRs), dihydralazine (25 mg kg-1, daily) and captopril (100 mg kg-1, daily) prevent with the same efficacy genetic hypertension development (GHD). Dihydralazine treatment increased vascular mesenteric compliance, as shown by a significant decrease in the stiffness of the vessels (-27%), and induced slight reductions in contractility (-12%) and in wall to lumen (W/L) ratio (-15%). After treatment withdrawal, all these parameters returned to control values within 7 weeks, as did blood pressure. Captopril treatment also strongly increased the mesenteric vessels compliance, vessel stiffness being decreased by 16%, and reduced their contractility (-15%) and their W/L ratio (-30%). These effects as well as those exerted on blood pressure persisted up to 7 weeks after treatment ceased although there was a slight trend to a progressive reduction in the intensity of both phenomena. These experiments show that captopril but not dihydralazine has a long-lasting effect in opposing the functional and morphological vascular alterations occurring during GHD in SHRs and this phenomenon probably contributes to a large extent to the sustained preventive effects of the drug against GHD. PMID:6357337

  20. Echocardiography in Pediatric Pulmonary Hypertension

    PubMed Central

    Jone, Pei-Ni; Ivy, D. Dunbar

    2014-01-01

    Pulmonary hypertension (PH) can be a rapidly progressive and fatal disease. Although right heart catheterization remains the gold standard in evaluation of PH, echocardiography remains an important tool in screening, diagnosing, evaluating, and following these patients. In this article, we will review the important echocardiographic parameters of the right heart in evaluating its anatomy, hemodynamic assessment, systolic, and diastolic function in children with PH. PMID:25429362

  1. Inhaled Therapies for Pulmonary Hypertension.

    PubMed

    Hill, Nicholas S; Preston, Ioana R; Roberts, Kari E

    2015-06-01

    The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies. PMID:26070575

  2. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary arterial hypertension associated with connective tissue diseases

    PubMed Central

    Boueiz, Adel; Hassoun, Paul M.

    2014-01-01

    The explosive growth of medical literature on pulmonary hypertension (PH) has led to a steady increase in awareness of this disease within the medical community during the past decade. The recent revision of the classification of PH is presented in in the main guidelines. Group 1 PH or pulmonary arterial hypertension (PAH) is a heterogeneous group and includes PH due to inheritable, drug-induced, and toxin-induced causes and to such underlying systemic causes as connective tissue diseases, human immunodeficiency viral infection, portal hypertension, congenital heart disease, and schistosomiasis. Systemic sclerosis (SSc) is an autoimmune multisystem disorder, which affects over 240 persons per million in the United States.[1] Its manifestations are not confined to the skin but may also involve the lungs, kidneys, peripheral circulation, musculoskeletal system, gastrointestinal tract, and heart. The outcome of PAH associated with SSc is worse when compared to other subtypes of PAH. In this review, we summarize available information about the pulmonary vascular and cardiac manifestations of SSc with special emphasis on their prognostic implications as well as the peculiarity of their detection. PMID:25076994

  3. Capsaicin and arterial hypertensive crisis.

    PubMed

    Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; La Rocca, Roberto

    2010-10-01

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment can deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs have significantly increased mean arterial blood pressure compared with controls, and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. A case has also been reported of an arterial hypertensive crisis in a patient with a large ingestion of peppers and chili peppers the day before. We present a case of an arterial hypertensive crisis in a 19-year-old Italian man with an abundant ingestion of peppers and of chili peppers the preceding day. This case describes an unusual pattern of arterial hypertensive crisis due to capsaicin. PMID:19168246

  4. Circulating and Vascular Bioactive Factors during Hypertension in Pregnancy

    PubMed Central

    Tanbe, Alain F.; Khalil, Raouf A.

    2010-01-01

    Normal pregnancy is associated with significant vascular remodeling in the uterine and systemic circulation in order to meet the metabolic demands of the mother and developing fetus. The pregnancy-associated vascular changes are largely due to alterations in the amount/activity of vascular mediators released from the endothelium, vascular smooth muscle and extracellular matrix. The endothelium releases vasodilator substances such as nitric oxide, prostacyclin and hyperpolarizing factor as well as vasoconstrictor factors such as endothelin, angiotensin II and thromboxane A2. Vascular smooth muscle contraction is mediated by intracellular free Ca2+ concentration ([Ca2+]i), and [Ca2+]i sensitization pathways such as protein kinase C, Rho-kinase and mitogen-activated protein kinase. Extracellular matrix and vascular remodeling are regulated by matrix metalloproteases. Hypertension in pregnancy and preeclampsia are major complications and life threatening conditions to both the mother and fetus, precipitated by various genetic, dietary and environmental factors. The initiating mechanism of preeclampsia and hypertension in pregnancy is unclear; however, most studies have implicated inadequate invasion of cytotrophoblasts into the uterine artery, leading to reduction in the uteroplacental perfusion pressure and placental ischemia/hypoxia. This placental hypoxic state is thought to induce the release of several circulating bioactive factors such as growth factor inhibitors, anti-angiogenic proteins, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and vascular receptor antibodies. Increases in the plasma levels and vascular content of these factors during pregnancy could cause an imbalance in the vascular mediators released from the endothelium, smooth muscle and extracellular matrix, and lead to severe vasoconstriction and hypertension. This review will discuss the interactions between the various circulating bioactive factors and the vascular mediators released during hypertension in pregnancy, and provide an insight into the current and future approaches in the management of preeclampsia. PMID:20419111

  5. Targeting cell motility in pulmonary arterial hypertension.

    PubMed

    Paulin, Roxane; Meloche, Jolyane; Courboulin, Audrey; Lambert, Caroline; Haromy, Alois; Courchesne, Antony; Bonnet, Pierre; Provencher, Steeve; Michelakis, Evangelos D; Bonnet, Sébastien

    2014-02-01

    Pulmonary artery smooth muscle cells (PASMC), in pulmonary arterial hypertension (PAH), contribute to obliterative vascular remodelling and are characterised by enhanced proliferation, suppressed apoptosis and, a much less studied, increased migration potential. One of the major proteins that regulate cell migration is focal adhesion kinase (FAK), but its role in PAH is not fully understood. We hypothesised that targeting cell migration by FAK inhibition may be a new therapeutic strategy in PAH. In vivo, inhalation of FAK-siRNA (n=5) or oral delivery of PF-228 (FAK inhibitor PF-573 228; n=5) inhibited rat monocrotaline induced PAH, improving the haemodynamics, vascular remodelling (media thickness), and right ventricular hypertrophy. In vitro, FAK was activated in PAH human lungs (n=8) or PASMC when compared to those form healthy subjects (Western blot, n=5), in a Src-dependent manner, as it was reversed by the specific Src inhibitor PP2. The degree of FAK phosphorylation at Y576 correlated positively with pulmonary vascular resistance in PAH patients. FAK inhibition (siRNA, PF-228 and PP2) in PAH-PASMCs induced a fivefold increase in apoptosis (percentage of terminal deoxynucleotidyl transferase dUTP nick end labelling), a 2.5-fold decrease in proliferation (%Ki67), an 18% decrease in cell migration (colorimetric assay) and a 50% decrease in cell invasion (wound healing). Suppressing PASMC migration by FAK inhibition inhibits PAH progression and may open a new therapeutic window in PAH. PMID:23845719

  6. Models of experimental hypertension in mice.

    PubMed

    Johns, C; Gavras, I; Handy, D E; Salomao, A; Gavras, H

    1996-12-01

    Experimental models of hypertension in various animals are useful in the research of vasoactive mechanisms. Recombinant DNA technology has produced genetically engineered animals, mostly mice, useful in hypertension research. However, the development of hypertensive models in mice is fraught with technical difficulties. We describe here the successful development in mice of two common types of experimental hypertension: the renovascular two-kidney, one clip and mineralocorticoid deoxycorticosterone-salt models. By adapting technology previously used in rats, we succeeded in developing hypertension (defined as systolic pressures higher than 140 mm Hg) in more than 50% of mice so treated. We also adapted the methodology for indirect tail-cuff blood pressure measurements as well as for direct intra-arterial monitoring of blood pressure in conscious, freely moving mice. Application of these techniques in transgenic or gene knockout mice with altered vasoactive hormones or receptors should allow elucidation of the role of the target gene products in various types of hypertension. PMID:8952597

  7. Tinnitus and arterial hypertension: a systematic review.

    PubMed

    Figueiredo, Ricardo Rodrigues; de Azevedo, Andréia Aparecida; Penido, Norma de Oliveira

    2015-11-01

    Tinnitus is considered a multi-factorial symptom. Arterial hypertension has been cited as a tinnitus etiological factor. To assess the scientific evidence on the associations between arterial hypertension and tinnitus. A systematic review was performed using PubMed, ISI Web, Lilacs and SciELO scientific databases. This review included articles published in Portuguese, Spanish, French and English correlating tinnitus with hypertension. Letters to editors and case reports were excluded. A total of 424 articles were identified, of which only 20 met the inclusion criteria. Studies that analyzed the incidence of hypertension in tinnitus patients tended to show an association, while those that evaluated the incidence of tinnitus in hypertensive patients did not. There is evidence of an association between tinnitus and hypertension, although a cause and effect relationship is uncertain. Changes in the cochlear microcirculation, resulting in hearing loss, may be an adjuvant factor in tinnitus pathophysiology. PMID:25190255

  8. (-)-Epigallocatechin-3-gallate decreases the impairment in learning and memory in spontaneous hypertension rats.

    PubMed

    Wang, Mao-Hsien; Chang, Wei-Jen; Soung, Hung-Sheng; Chang, Kuo-Chi

    2012-12-01

    Oxidative stress induced by hypertension has been reported to cause alterations in neural cytoarchitecture and cognitive dysfunction. Green tea catechins, especially (-)-epigallocatechin-3-gallate (EGCG), have potent antioxidative properties and protect against various oxidative damages. In this study, we examined the impact of hypertension in rats on locomotor activity, learning, and memory, and EGCG was tested for its potential therapeutic effects in treating hypertension-induced impairment. Blood pressure was measured by the tail-cuff method to confirm high blood pressure in spontaneous hypertension rats (SHRs). Locomotor activity in the open field was increased in SHRs, along with learning and memory impairment in the Morris water maze. Daily EGCG treatment reduced the progressive increase in blood pressure in SHRs, and prevented most of the increased locomotor activity in addition to improving learning and memory. EGCG treatment also decreased the increased level of lipid peroxide production in SHRs and enhanced the antioxidation power in plasma that was observed to be decreased in SHRs. EGCG also decreased the concentration of reactive oxygen species in the hippocampi of SHRs. These indicate a therapeutic effect of EGCG in treating hypertension-induced learning and memory impairment, most probably through its powerful antioxidative properties. PMID:23044831

  9. Hyperglycemia and Renin-Dependent Hypertension Synergize to Model Diabetic Nephropathy

    PubMed Central

    Rennie, Jillian; Bailey, Matthew A.; Dunbar, Donald R.; Manning, Jonathan R.; Bellamy, Christopher O.; Hughes, Jeremy; Mullins, John J.

    2012-01-01

    Rodent models exhibit only the earliest features of human diabetic nephropathy, which limits our ability to investigate new therapies. Hypertension is a prerequisite for advanced diabetic nephropathy in humans, so its rarity in typical rodent models may partly explain their resistance to nephropathy. Here, we used the Cyp1a1mRen2 rat, in which the murine renin-2 gene is incorporated under the Cytochrome P4501a1 promoter. In this transgenic strain, administration of low-dose dietary indole-3-carbinol induces moderate hypertension. In the absence of hypertension, streptozotocin-induced diabetes resulted in a 14-fold increase in albuminuria but only mild changes in histology and gene expression despite 28 weeks of marked hyperglycemia. In the presence of induced hypertension, hyperglycemia resulted in a 500-fold increase in albuminuria, marked glomerulosclerosis and tubulointerstitial fibrosis, and induction of many of the same pathways that are upregulated in the tubulointerstitium in human diabetic nephropathy. In conclusion, although induction of diabetes alone in rodents has limited utility to model human diabetic nephropathy, renin-dependent hypertension and hyperglycemia synergize to recapitulate many of the clinical, histological, and gene expression changes observed in humans. PMID:22193383

  10. Borderline hypertension. Circulatory, sympatho-adrenal and psychological reactions to stress.

    PubMed

    Eliasson, K

    1985-01-01

    The purpose of this study was to examine circulatory and sympatho-adrenal responsiveness in borderline hypertensives compared to established hypertensives and normotensive controls under conditions of physical and mental provocation. Measurements of plasma catecholamines or the urinary excretion of their metabolites were used as indicators of sympathetic activity and psychological variables were assessed by means of self-ratings. There were several signs of an increased neurogenic influence in borderline hypertensives. Urinary catecholamine excretion was related to body measures only in this group. During mental stress, induced by a filmed version of Stroop's colour word test, there were signs of an enhanced hypothalamic defence reaction in the borderline group, as judged by increased circulatory responses and higher plasma adrenaline levels. These signs of increased arousal could be associated with a tendency to compensate for a slightly decreased accuracy in task performance compared to controls by increasing effort. This led to a negative relationship between subjective stress and performance, present only in the borderline group. In another group of borderline hypertensives, the effects of personal control over work pace were compared to normotensives. Personal control reduced circulatory responses to mental arithmetics in controls, but had no beneficial effect in the borderline group. Also in this study, there were signs of an enhanced defence reaction in borderline hypertensives. Higher arousal levels in borderline hypertensives may, theoretically, be explained by personality differences. During an isometric handgrip test, borderline hypertensives showed a tendency towards increased alpha-adrenergic vasoconstriction compared to both established hypertensives and controls. A somewhat higher diastolic blood pressure variability, lower plasma volume and higher venous tone compared to normal also suggest increased neurogenic influences in borderline hypertension. There are similarities between the borderline hypertensive state and the circulatory and sympatho-adrenal pattern of the hypothalamic defence reaction. An enhancement of this reaction is particularly evident during mental stress, whereas somatic provocations such as an orthostatic test, a cold pressor test and physical work produce more similar responses compared to established hypertensives and controls. An increased reactivity to mental stress, especially when personal initiative is challenged, may contribute to the increased cardio-vascular morbidity of borderline hypertensives as a group. PMID:3883705

  11. Postoperative hypertension after radical neck dissection.

    PubMed

    Celikkanat, S; Akyol, M U; Koç, C; Olçer, S; Ensari, S; Turgut, S; Ozdem, C

    1997-07-01

    Postoperative hypertension after radical neck dissection was detected in 20.2% of 109 neck dissections in our department between 1989 and 1993. It was probably caused by carotid sinus denervation and appeared after the vasodilation generated by anesthesia had subsided. If postoperative hypertension was encountered after the first operation, the risk of such hypertension after surgery on the contralateral side significantly increased. PMID:9230330

  12. Renin in differential diagnosis of hypertension.

    NASA Technical Reports Server (NTRS)

    Oparil, S.; Haber, E.

    1971-01-01

    Renin is a proteolytic enzyme secreted by the kidney. Techniques for the direct measurement of renin content of human blood are not available at the present time. Two of the best known causes of remediable hypertension can be diagnosed from abnormalities in renin activity and aldosterone production. In renovascular hypertension, renin secretion is increased because of impaired glomerular perfusion. The renin activity assay, when applied in a carefully controlled fashion, is a useful screening test for treatable causes of hypertension.

  13. Evidence-Based Chinese Medicine for Hypertension

    PubMed Central

    Wang, Jie; Xiong, Xingjiang

    2013-01-01

    Hypertension is an important worldwide public -health challenge with high mortality and disability. Due to the limitations and concerns with current available hypertension treatments, many hypertensive patients, especially in Asia, have turned to Chinese medicine (CM). Although hypertension is not a CM term, physicians who practice CM in China attempt to treat the disease using CM principles. A variety of approaches for treating hypertension have been taken in CM. For seeking the best evidence of CM in making decisions for hypertensive patients, a number of clinical studies have been conducted in China, which has paved the evidence-based way. After literature searching and analyzing, it appeared that CM was effective for hypertension in clinical use, such as Chinese herbal medicine, acupuncture, moxibustion, cupping, qigong, and Tai Chi. However, due to the poor quality of primary studies, clinical evidence is still weak. The potential benefits and safety of CM for hypertension still need to be confirmed in the future with well-designed RCTs of more persuasive primary endpoints and high-quality SRs. Evidence-based Chinese medicine for hypertension still has a long way to go. PMID:23861720

  14. The Management of Hypertension in Pregnancy

    PubMed Central

    Kattah, Andrea G.; Garovic, Vesna D.

    2014-01-01

    Hypertensive pregnancy disorders complicate 6–8% of pregnancies and cause significant maternal and fetal morbidity and mortality. The goal of treatment is to prevent significant cerebrovascular and cardiovascular events in the mother, without compromising fetal well-being. Current guidelines differentiate between the treatment of women with acute hypertensive syndromes of pregnancy and women with preexisting chronic hypertension in pregnancy. This review will address the management of hypertension in pregnancy, review the various pharmacologic therapies, and discuss the future directions in this field. PMID:23928387

  15. Elevated Ecto-5’-nucleotidase-Mediated Increased Renal Adenosine Signaling Via A2B Adenosine Receptor Contributes to Chronic Hypertension

    PubMed Central

    Zhang, Weiru; Zhang, Yujin; Wang, Wei; Dai, Yingbo; Ning, Chen; Luo, Renna; Sun, Kaiqi; Glover, Louise; Grenz, Almut; Sun, Hong; Tao, Lijian; Zhang, Wenzheng; Colgan, Sean P.; Blackburn, Michael R.; Eltzschig, Holger K.; Kellems, Rodney E.; Xia, Yang

    2013-01-01

    Rationale Hypertension is the most prevalent life-threatening disease worldwide and is frequently associated with chronic kidney disease (CKD). However, the molecular basis underlying hypertensive CKD is not fully understood. Objective We sought to identify specific factors and signaling pathways that contribute to hypertensive CKD and thereby exacerbate disease progression. Methods and Results Using high-throughput quantitative reverse-transcription polymerase chain reaction profiling, we discovered that the expression level of 5?-ectonucleotidase (CD73), a key enzyme that produces extracellular adenosine, was significantly increased in the kidneys of angiotensin II–infused mice, an animal model of hypertensive nephropathy. Genetic and pharmacological studies in mice revealed that elevated CD73-mediated excess renal adenosine preferentially induced A2B adenosine receptor (ADORA2B) production and that enhanced kidney ADORA2B signaling contributes to angiotensin II–induced hypertension. Similarly, in humans, we found that CD73 and ADORA2B levels were significantly elevated in the kidneys of CKD patients compared with normal individuals and were further elevated in hypertensive CKD patients. These findings led us to further discover that elevated renal CD73 contributes to excess adenosine signaling via ADORA2B activation that directly stimulates endothelin-1 production in a hypoxia-inducible factor-?–dependent manner and underlies the pathogenesis of the disease. Finally, we revealed that hypoxia-inducible factor-? is an important factor responsible for angiotensin II–induced CD73 and ADORA2B expression at the transcriptional level. Conclusions Overall, our studies reveal that angiotensin II–induced renal CD73 promotes the production of renal adenosine that is a prominent driver of hypertensive CKD by enhanced ADORA2B signaling–mediated endothelin-1 induction in a hypoxia-inducible factor-?–dependent manner. The inhibition of excess adenosine-mediated ADORA2B signaling represents a novel therapeutic target for the disease. PMID:23584256

  16. Genetic and Functional Evidence Supports LPAR1 as a Susceptibility Gene for Hypertension.

    PubMed

    Xu, Ke; Ma, Lu; Li, Yang; Wang, Fang; Zheng, Gu-Yan; Sun, Zhijun; Jiang, Feng; Chen, Yundai; Liu, Huirong; Dang, Aimin; Chen, Xi; Chun, Jerold; Tian, Xiao-Li

    2015-09-01

    Essential hypertension is a complex disease affected by genetic and environmental factors and serves as a major risk factor for cardiovascular diseases. Serum lysophosphatidic acid correlates with an elevated blood pressure in rats, and lysophosphatidic acid interacts with 6 subtypes of receptors. In this study, we assessed the genetic association of lysophosphatidic acid receptors with essential hypertension by genotyping 28 single-nucleotide polymorphisms from genes encoding for lysophosphatidic acid receptors, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6 and their flanking sequences, in 3 Han Chinese cohorts consisting of 2630 patients and 3171 controls in total. We identified a single-nucleotide polymorphism, rs531003 in the 3'-flanking genomic region of LPAR1, associated with hypertension (the Bonferroni corrected P=1.09×10(-5), odds ratio [95% confidence interval]=1.23 [1.13-1.33]). The risk allele C of rs531003 is associated with the increased expression of LPAR1 and the susceptibility of hypertension, particularly in those with a shortage of sleep (P=4.73×10(-5), odds ratio [95% confidence interval]=1.75 [1.34-2.28]). We further demonstrated that blood pressure elevation caused by sleep deprivation and phenylephrine-induced vasoconstriction was both diminished in LPAR1-deficient mice. Together, we show that LPAR1 is a novel susceptibility gene for human essential hypertension and that stress, such as shortage of sleep, increases the susceptibility of patients with risk allele to essential hypertension. PMID:26123684

  17. Independent Influence of Overweight and Obesity on the Regression of Left Ventricular Hypertrophy in Hypertensive Patients

    PubMed Central

    Zhang, Kun; Huang, Feifei; Chen, Jie; Cai, Qingqing; Wang, Tong; Zou, Rong; Zuo, Zhiyi; Wang, Jingfeng; Huang, Hui

    2014-01-01

    Abstract Overweight and obesity are associated with adverse cardiovascular outcomes. However, the role of overweight and obesity in left ventricular hypertrophy (LVH) of hypertensive patients is controversial. The aim of the current meta-analysis was to evaluate the influence of overweight and obesity on LVH regression in the hypertensive population. Twenty-eight randomized controlled trials comprising 2403 hypertensive patients (mean age range: 43.8–66.7 years) were identified. Three groups were divided according to body mass index: normal weight, overweight, and obesity groups. Compared with the normal-weight group, LVH regression in the overweight and obesity groups was more obvious with less reduction of systolic blood pressure after antihypertensive therapies (P?hypertensive patients (19.27?g/m2, 95% confidence interval [15.25, 23.29], P?hypertensive patients. Intervention at an early age and monitoring by ABPM may facilitate therapy-induced LVH regression in overweight and obese hypertensive patients. PMID:25437025

  18. The toll of the gridiron: damage-associated molecular patterns and hypertension in American football.

    PubMed

    McCarthy, Cameron G; Webb, R Clinton

    2016-01-01

    American football has unequivocally been linked to elevations in blood pressure and hypertension, especially in linemen. However, the mechanisms of this increase cannot be attributed solely to increased body weight and associated cardiometabolic risk factors (e.g.,dyslipidemia or hyperglycemia). Therefore, understanding the etiology of football-associated hypertension is essential for improving the quality of life in this mostly young population, as well as for lowering the potential for chronic disease in the future. We propose that inflammatogenic damage-associated molecular patterns (DAMPs) released into the circulation from football-induced musculoskeletal trauma activate pattern-recognition receptors of the innate immune system-specifically, high mobility group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like receptor (TLR)4 and -9, respectively. Previously, we observed that circulating levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and -9 causes endothelial dysfunction and hypertension. Therefore, our novel hypothesis is that musculoskeletal injury from repeated hits in football players, particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to activate TLRs on endothelial cells leading to impaired endothelium-dependent vasodilation, increased vascular tone, and hypertension.-McCarthy, C. G., Webb, R. C. The toll of the gridiron: damage-associated molecular patterns and hypertension in American football. PMID:26316270

  19. Consistent antioxidant and antihypertensive effects of oral sodium nitrite in DOCA-salt hypertension

    PubMed Central

    Amaral, Jefferson H.; Ferreira, Graziele C.; Pinheiro, Lucas C.; Montenegro, Marcelo F.; Tanus-Santos, Jose E.

    2015-01-01

    Hypertension is a common disease that includes oxidative stress as a major feature, and oxidative stress impairs physiological nitric oxide (NO) activity promoting cardiovascular pathophysiological mechanisms. While inorganic nitrite and nitrate are now recognized as relevant sources of NO after their bioactivation by enzymatic and non-enzymatic pathways, thus lowering blood pressure, mounting evidence suggests that sodium nitrite also exerts antioxidant effects. Here we show for the first time that sodium nitrite exerts consistent systemic and vascular antioxidant and antihypertensive effects in the deoxycorticosterone-salt (DOCA-salt) hypertension model. This is particularly important because increased oxidative stress plays a major role in the DOCA-salt hypertension model, which is less dependent on activation of the renin-angiotensin system than other hypertension models. Indeed, antihypertensive effects of oral nitrite were associated with increased plasma nitrite and nitrate concentrations, and completely blunted hypertension-induced increases in plasma 8-isoprostane and lipid peroxide levels, in vascular reactive oxygen species, in vascular NADPH oxidase activity, and in vascular xanthine oxidoreductase activity. Together, these findings provide evidence that the oral administration of sodium nitrite consistently decreases the blood pressure in association with major antioxidant effects in experimental hypertension. PMID:26119848

  20. Haemodynamic effects of chronic octreotide and tetrandrine administration in portal hypertensive rats.<