scholarly journals Glucocorticoid receptor polymorphism in genetic hypertension

1998 ◽  
Vol 21 (1) ◽  
pp. 41-50 ◽  
Author(s):  
CJ Kenyon ◽  
M Panarelli ◽  
L Zagato ◽  
L Torielli ◽  
RP Heeley ◽  
...  

The Milan hypertensive strain of rat (MHS) displays abnormalities in both renal function and adrenocortical activity. While the pressor role of the former has been studied in detail, the role of the latter has not yet been clearly evaluated. In the present study, glucocorticoid receptor (GR) binding characteristics in liver cytosol from adult MHS and Milan normotensive controls (MNS) have been investigated. Dexamethasone, aldosterone and corticosterone were bound with lower affinity to cytosol of MHS rats compared with that of MNS rats. This pattern of binding could explain the raised plasma corticosterone concentrations and adrenocortical hypertrophy previously noted in MHS. The coding sequence of MHS and MNS GR genes have been determined. The MHS gene differed in four respects from that of MNS: three silent point mutations and a polymorphic microsatellite region in exon 2. The latter polymorphism has been used in cosegregation studies of F2 hybrids of MHS x MNS. The MHS GR genotype was associated with hypercalciuria and lower blood pressure in female rats and lower body weight in male rats. Although the effect on blood pressure is small, it is consistent with the affinity data. MHS GR genotype cosegregated with lower blood pressure in F2 rats and displayed a lower affinity in binding studies. In conclusion, GR polymorphism may be responsible for differences of adrenocortical function between MHS and MNS. This may lead to a reduction in the blood pressure difference between the two strains.

Author(s):  
Oryza Sativa Fitriani ◽  
Suhatri Suhatri ◽  
Harrizul Rivai

Traditional medicinal ingredients originating from the Province of East Kalimantan (Indonesia) with the composition of meniran leaves (Phyllanthus niruri L.), cat whiskers leaves (Orthosiphon aristatus), ceplukan leaves (Physalis minima L.), and lempuyang emprit rhizome (Zingiberis amaricana Bl.) are used to help lower blood pressure by the local community. This study aimed to analyze the content of chemical compounds, determine the levels of chemical compounds, and the antihypertensive effect of these traditional medicinal ingredients. This traditional medicinal herb is made into a fine powder and then brewed with boiling water. Phytochemical screening and determination of levels of phytochemical compounds were carried out on these traditional medicinal ingredients. Testing the antihypertensive effect of these traditional medicinal ingredients was carried out on white male rats. The results of the qualitative analysis showed that the chemical compounds contained in the traditional medicinal ingredients were flavonoids, phenols, tannins, and carbohydrates. Quantitative analysis of the traditional medicinal ingredients showed that the content of flavonoid compounds was 0.6375%, phenolic compounds were 3.2412%, and tannin compounds were 0.6593%. Testing the antihypertensive effect of this traditional medicinal herb on rats can reduce systolic, diastolic, and arterial blood pressure. The conclusion is that this traditional medicinal herb contains phytochemical compounds that can help lower blood pressure in rats.


1989 ◽  
Vol 66 (4) ◽  
pp. 1730-1735 ◽  
Author(s):  
C. A. Tozzi ◽  
G. J. Poiani ◽  
N. H. Edelman ◽  
D. J. Riley

We studied the role of vascular collagen on the responsiveness of isolated pulmonary arteries to vasoactive agonists. Dose-response curves to prostaglandin F2 alpha, (PGF2 alpha), angiotensin II (ANG II), and norepinephrine (NE) and responses to a depolarizing concentration of KCl were obtained on rings of pulmonary artery from normal rats, chronically hypoxic (10% O2 for 10 days) rats, and chronically hypoxic rats treated with cis-4-hydroxy-L-proline (cHyp), an agent that blocks collagen accumulation. Treatment with this agent prevented the rise in pulmonary blood pressure normally seen during hypoxia. Collagen content was twice normal in hypoxic vessels and was significantly reduced in vessels from cHyp-treated hypoxic rats. There was no change in reactivity to PGF2 alpha, but reactivity to ANG II, NE, and KCl was decreased in vessels from hypoxic rats. cHyp treatment completely restored reactivity to NE and KCl and partially restored reactivity to ANG II. The changes in contractility could be a response to the lower blood pressure. Another explanation is that collagen deposited in hypertensive pulmonary arteries may impair reactivity to some constrictor agonists.


2016 ◽  
Vol 311 (1) ◽  
pp. F71-F77 ◽  
Author(s):  
Carolina Dalmasso ◽  
Rodrigo Maranon ◽  
Chetan Patil ◽  
Mohadetheh Moulana ◽  
Damian G. Romero ◽  
...  

In male rats, androgen supplements increase 20-hydroxyeicosatetraenoic acid (20-HETE) via cytochrome P-450 (CYP)4A ω-hydroxylase and cause an increase in blood pressure (BP). In the present study, we determined the roles of 20-HETE and CYP4A2 on the elevated BP in hyperandrogenemic female rats. Chronic dihydrotestosterone (DHT) increased mean arterial pressure (MAP) in female Sprague-Dawley rats (96 ± 2 vs. 108 ± 2 mmHg, P < 0.05) and was associated with increased renal microvascular CYP4A2 mRNA expression (15-fold), endogenous renal 20-HETE (5-fold), and ω-hydroxylase activity (3-fold). Chronic DHT also increased MAP in low salt-fed Dahl salt-resistant female rats (81 ± 4 vs. 95 ± 1 mmHg, P < 0.05) but had no effect on MAP in Dahl salt-sensitive female rats (154 ± 3 vs. 153 ± 3 mmHg), which are known to be 20-HETE deficient. To test the role of CYP4A2, female CYP4A2−/− and SS.5Bn (wild type) rats were treated with DHT. DHT increased MAP in SS.5Bn female rats (104 ± 1 vs. 128 ± 1 mmHg, P < 0.05) but had no effect in CYP4A2−/− female rats (118 ± 1 vs. 120 ± 1 mmHg). Renal microvascular 20-HETE was reduced in control CYP4A2−/− female rats and was increased with DHT in SS.5Bn female rats (6-fold) but not CYP4A2−/− female rats. ω-Hydroxylase activity was 40% lower in control CYP4A2−/− female rats than in SS.5Bn female rats, and DHT decreased ω-hydroxylase activity in SS.5Bn female rats (by 50%) but significantly increased ω-hydroxylase activity in CYP4A2−/− female rats (3-fold). These data suggest that 20-HETE via CYP4A2 contributes to the elevation in BP in hyperandrogenemic female rats. The data also suggest that 20-HETE synthesis inhibition may be effective in treating the elevated BP in women with hyperandrogenemia, such as women with polycystic ovary syndrome.


1987 ◽  
Vol 21 (3) ◽  
pp. 577-591 ◽  
Author(s):  
Anthony Walsh ◽  
Patricia Ann Walsh

This study explores the role of social support on blood pressure levels among a sample of immigrants. The measure of blood pressure used is biological effective blood pressure, a mathematically transformed single measure derived from systolic and diastolic readings. The twin processes of immigration and assimilation are highly stressful. Stress is a major precursor of elevated blood pressure. It is assumed here that assimilation is differentially stressful according to the amount of social support one receives. Protracted stress will be manifested in elevated blood pressure levels. We found that social support was second only to age in its ability to account independently for variance in blood pressure levels. Immigrants receiving high levels of social support had significantly lower blood pressure levels than those receiving less social support. Social support was also significantly related to assimilation.


2014 ◽  
Vol 306 (8) ◽  
pp. H1146-H1153 ◽  
Author(s):  
Dong Sun ◽  
Azita J. Cuevas ◽  
Katherine Gotlinger ◽  
Sung Hee Hwang ◽  
Bruce D. Hammock ◽  
...  

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid via cytochrome P450 (CYP)/epoxygenases. EETs possess cardioprotective properties and are catalyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs) that lack vasoactive property. To date, the role of sEH in the regulation of myogenic response of resistant arteries, a key player in the control of blood pressure, remains unknown. To this end, experiments were conducted on sEH-knockout (KO) mice, wild-type (WT) mice, and endothelial nitric oxide synthase (eNOS)-KO mice treated with t-TUCB, a sEH inhibitor, for 4 wk. sEH-KO and t-TUCB-treated mice displayed significantly lower blood pressure, associated with significantly increased vascular EETs and ratio of EETs/DHETs. Pressure-diameter relationships were assessed in isolated and cannulated gracilis muscle arterioles. All arterioles constricted in response to increases in transmural pressure from 60 to 140 mmHg. The myogenic constriction was significantly reduced, expressed as an upward shift of pressure-diameter curve, in arterioles of sEH-KO and t-TUCB-treated eNOS-KO mice compared with their controls. Removal of the endothelium, or treatment of the vessels with PPOH, an inhibitor of EET synthase, restored the attenuated pressure-induced constriction to the levels similar to those observed in their controls but had no effects on control vessels. No difference was observed in the myogenic index, or in the vascular expression of eNOS, CYP2C29 (EET synthase), and CYP4A (20-HETE synthase) among these groups of mice. In conclusion, the increased EET bioavailability, as a function of deficiency/inhibition of sEH, potentiates vasodilator responses that counteract pressure-induced vasoconstriction to lower blood pressure.


2020 ◽  
pp. 51-57
Author(s):  
S. R. Gilyarevsky ◽  
M. V. Golshmid ◽  
N. G. Bendeliani ◽  
I. M. Kuzmina ◽  
G. Y. Zaharova ◽  
...  

The article discusses the vascular age concept and modern approaches to assessing vascular age. It describes modern methods for measuring arterial stiffness (applanation tonometry or ultrasonic Doppler examination) as the most frequently used index of vascular age. The authors discuss the role of antihypertensive therapy and statins in preventing early vascular aging, and the relationship between the role of achieving lower blood pressure levels and the choice of certain antihypertensive agents to reduce arterial stiffness and ensure optimal vascular age. Increased arterial stiffness has been reported to be a marker of risk for developing severe complications of cardiovascular diseases, in particular, a meta-analysis showed that after taking into account the known risk factors for developing cardiovascular complications, higher carotid stiffness was associated with an increased risk of stroke. It is stated that in addition to biological age, vascular age may increase due to the cumulative effect of such risk factors as high blood pressure, impaired glucose homeostasis, obesity and hypercholesterolemia. Modern approaches to the preservation and maintenance of vascular age are discussed. The key role of achieving lower blood pressure levels is considered. It is emphasized that the role of combination drugs in preventing complications of cardiovascular diseases is strengthened, and approaches to choosing the optimal components of such combination drugs are also considered. The relationship between increased arterial stiffness and the development of cognitive disorders is discussed. The article describes the role of statins and effectiveness of the concomitant use of statins and combination antihypertensive therapy in reducing the pulse wave velocity.


Sign in / Sign up

Export Citation Format

Share Document