C1166 POLYMORPHISM OF ANGIOTENSIN II TYPE 1 RECEPTOR (AT1R) GENE & ITS ASSOCIATION WITH AORTIC STIFFNESS, BLOOD PRESSURE, ANTHROPOMETRIC MEASUREMENTS & TOTAL CHOLESTEROL AMONG TREATED MALAY HYPERTENSIVES & NORMOTENSIVE SUBJECTS

P17 Objective: The C allele of the angiotensin II type 1 receptor (AT1R) A1166C polymorphism has been associated in several studies with increased risks of hypertension (HTN) and myocardial infarction (MI), and with enhanced blood pressure (BP) response to ACE inhibitors but not calcium antagonists. Most of these studies were small, and none included large numbers of African Americans. We examined these associations in the Cardiovascular Health Study, an observational cohort study of risk factors for coronary disease and stroke in men and women ≥ 65 years of age. Methods: All 771 self-identified African Americans plus 1333 randomly-selected Caucasians were genotyped for the AT1R polymorphism. BP, medication use, and HTN were assessed annually. Incident MI/coronary death (CHD, n = 125 in whites; n = 60 in blacks), incident total cardiovascular events (CVD, n = 226 in whites; n = 101 in blacks), incident congestive heart failure (CHF, n = 146 in whites; n = 55 in blacks), and incident HTN (n = 184 in whites; n = 85 in blacks) were identified during up to 8 years of follow-up. Results: Genotype frequency distributions differed between whites (AA 49%, AC 41%, CC 10%) and blacks (85%, 15%, 1%, p < 0.0005). Age, gender or HTN at baseline did not differ by genotype in either group. In both whites and blacks, genotype was not associated with incident CHD (HR for AC/CC vs. AA, 95% CI in whites = 1.0, 0.7-1.5; blacks, HR = 0.7, 0.3-1.5), incident total CVD events (whites, HR = 1.0, 0.8-1.3; blacks, HR = 0.9, 0.5-1.6), incident CHF (whites, HR = 1.1, 0.8-1.5; blacks, 0.6, 0.3-1.4) or newly-identified HTN (whites, HR = 0.8, 0.6-1.1; blacks, HR = 1.1, 0.6-1.9). Among treated hypertensives, the association of genotype with controlled BP (<140/<90) did not differ between users of calcium channel blockers and users of ACE inhibitors in either race. Conclusion: In this large population-based elderly cohort, the AT1R A1166C polymorphism was not associated with prevalent or newly-identified HTN, incident CVD events, or BP response to antihypertensive agents in either Caucasians or African Americans.

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Effects of Prehypertensive Losartan Treatment on Resistance Vessel Remodeling and Angiotensin II Type 1 Receptor Expression in Spontaneously Hypertensive Rats

American Journal of Hypertension ◽

10.1093/ajh/hpaa008 ◽

2020 ◽

Vol 33 (5) ◽

pp. 471-471

Author(s):

Ting-jun Wang ◽

Wan-ru Chen ◽

Xu Lin ◽

Gui-li Lian ◽

Chang-sheng Xu ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Receptor Expression ◽

Mesenteric Arteries ◽

Resistance Vessel ◽

Spontaneously Hypertensive ◽

Vessel Remodeling ◽

Wistar Kyoto ◽

Losartan Treatment

Abstract Background To study the effects of prehypertensive losartan treatment on blood pressure, resistance vessel remodeling, and angiotensin II type 1 receptor (AT1R) expression in adult spontaneously hypertensive rats (SHRs). Methods Four-week-old SHR and Wistar-Kyoto rats were randomly divided into losartan-treated and untreated groups. Losartan was administrated by gavage from 4 to 10 weeks old. Blood pressure was monitored by the tail-cuff method till 26 weeks old. The third grade mesenteric arteries were then isolated. Vessel structure, relaxation reactivity, angiotensin II type 1 receptor expression, and angiotensin II levels were analyzed. Results Losartan treatment from 4 to 10 weeks of age significantly lowered systolic blood pressure from 10 to 26 weeks in SHR. At 26 weeks old, wall thickness to lumen radius and wall area to lumen area of mesenteric arteries were significantly lower in losartan-treated than untreated SHR (P < 0.01). Maximum relaxation to acetylcholine and its pD2 were increased in losartan-treated compared to untreated SHR (P < 0.01). Angiotensin II type 1 receptor mRNA and protein levels were significantly reduced in losartan-treated SHR (P < 0.01). However, angiotensin II levels in plasma and mesenteric arteries of losartan-treated SHR were higher than those of untreated SHR (P < 0.05). Losartan treatment lowered systolic blood pressure in Wistar-Kyoto at the age of 10 weeks (P < 0.05), but had no significant effect on blood pressure after 14 weeks or mesenteric arteries at 26 weeks. Conclusions Blood pressure reduction induced by prehypertensive losartan treatment ameliorates resistance vessel remodeling and downregulates angiotensin II type 1 receptor expression in adult SHR.

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Angiotensin II Type 1 Receptor Binding Molecule ATRAP as a Possible Modulator of Renal Sodium Handling and Blood Pressure in Pathophysiology

Current Medicinal Chemistry ◽

10.2174/0929867322666150821095036 ◽

2015 ◽

Vol 22 (28) ◽

pp. 3210-3216 ◽

Cited By ~ 12

Author(s):

K. Tamura ◽

H. Wakui ◽

K. Azushima ◽

K. Uneda ◽

S. Haku ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Receptor Binding ◽

Renal Sodium Handling ◽

Sodium Handling

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A1166C polymorphism of angiotensin II type 1 receptor, blood pressure and arterial stiffness in hypertension

Journal of Hypertension ◽

10.1097/00004872-200411000-00016 ◽

2004 ◽

Vol 22 (11) ◽

pp. 2135-2142 ◽

Cited By ~ 21

Author(s):

St??phany Gardier ◽

Madeleine Vincent ◽

Pierre Lantelme ◽

Marie-Odile Rial ◽

Giampiero Bricca ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Arterial Stiffness ◽

A1166c Polymorphism

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Abstract 142: Angiotensin II Type 1 Receptor Autoantibody Inhibition Improves Blood Pressure and Markers of Neurological Damage and Oxidative Stress in Brains of Placental Ischemic Rats During Pregnancy

Hypertension ◽

10.1161/hyp.70.suppl_1.142 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Mark W Cunningham ◽

Venkata Ramana Vaka ◽

Lorena Amaral ◽

Fan Fan ◽

Tarek Ibrahim ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Angiotensin Ii ◽

Nadph Oxidase ◽

Oxidase Activity ◽

Neurological Complications ◽

Peptide Sequence ◽

Inhibitory Peptide ◽

Nadph Oxidase Activity

Preeclampsia (PE), hypertension in response to placental ischemia, is associated with angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA), oxidative stress, and neurological complications, such as headaches, blurred vision, and seizures which could lead to stroke and death. We hypothesize that AT1AAs play a role in the cerebral pathology of PE. The objective of this study was to determine if administration of a specific peptide sequence to inhibit the AT1-AA from binding to the AT1 receptor, will improve blood pressure (MAP) and cerebral oxidative stress in the reduced uterine perfusion pressure (RUPP) rat model of PE. Pregnant Sprague Dawley rats were divided into 2 groups: RUPP (n=5) and RUPP+AT1-AA inhibitory peptide (7AA) (n=3). RUPP surgery was performed on gestational day (GD) 14 and the 7AA was administered (2ug/μl saline) via mini-osmotic pumps. On GD 19, MAP was determined and brains collected. Western blots were stained for Glial Fibrillary Acidic Protein (GFAP), endothelial NO synthase (eNOS), phosphorylated eNOS and NADPH oxidase activity was determined using chemilumenescence. MAP was decreased in RUPP+7AA vs. RUPP (95±2 vs. 130±6 mmHg). Brain/body weight ratio, which is indicative of edema, was reduced in RUPP+7AA (5.8±0.25 vs. 6.5±0.25 grams) vs. RUPP. NADPH oxidase activity was lower in RUPP+7AA (33275±3122 vs. 57408±10508 RLU/min/mg protein). Phosphorylated eNOS was 2 fold higher in the RUPP+7AA vs. RUPP (0.4±0.1 vs. 0.2±0.04 AU) and the phosphorylated eNOS/eNOS ratio was elevated (0.4±0.12 vs. 0.2±0.04 AU). GFAP a marker for activated astrocytes that increases during neurologic injury and serves as a compensatory mechanism for brain injury recovery was elevated in RUPP+7AA vs. RUPP (3.2±1.3 vs. 0.5±0.2 AU). Administration of AT1-AA inhibitory peptide to RUPP rats decreased blood pressure and improved markers of NO bioavailability, injury (GFAP), and cerebral swelling. In conclusion, our preliminary data suggests that AT1-AA inhibition could be a potential therapy to improve peripheral and neurological complications during PE. Research Supported by T32HL105324 (Cunningham), RO1HD067541-06 (LaMarca), DK-104184 (Roman), 050049 (Fan), P20-GM-104357 (cores B and C-Roman; Pilot-Fan) and AHA 16GRNT31200036 (Fan).

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Abstract P231: Offspring of Captopril Treated Spontaneously Hypertensive Rats Have Lower Angiotensin II Type 1 Receptor Expression Which is Associated With Lower Blood Pressure

Hypertension ◽

10.1161/hyp.70.suppl_1.p231 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

J X Masjoan-Juncos ◽

Tang-Dong Liao ◽

Ginette Bordcoch ◽

Cesar A Romero ◽

Oscar A Carretero

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Posterior Wall ◽

Receptor Expression ◽

Shr Rats ◽

Spontaneously Hypertensive ◽

Intracerebroventricular Infusion ◽

Lower Blood ◽

The Brain

It has been reported that SHR rats receiving angiotensin converting enzyme (ACE) inhibitor Captopril decrease blood pressure (BP) in at least two generation after the treatment was stopped. A decreased response to an intracerebroventricular infusion angiotensin I and angiotensin II in treated animals and their offspring was reported; however there is no reported mechanism that explains the changes observed in the untreated offspring of the Captopril treated animals. We hypothesize that captopril reduces angiotensin II type 1 receptor (AT1R) expression in CNS of the offspring of SHR rats treated with captopril. Animal groups are as follows: control animals, captopril treated animals, offspring of the control animals, offspring of the treated animals where the mother was removed from the treatment immediately after giving birth and Offspring of treated animals where the mother was removed from the treatment at weaning. BP was measured by intra-arterial method and Tail cuff. AT1R expression was measured in brain tissue using the posterior wall of the forth ventricle, as well as the top half of the brain stem. BP was different between treated groups and their offspring vs. control (Table 1). AT1R expression was significantly reduced in both offspring groups of the treated animals, when compared to control (Table 1). Therefore we conclude that captopril reduces blood pressure in the offspring of captopril treated SHR rats and that associates with a decrease in AT1R expression in CNS. Further research is necessary to determine the possible epigenetic mechanisms involved in AT1R reduction.

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Abstract 3636: Ekg Left Ventricular Hypertrophy And Cardiovascular Events In Patients With Type 1 And Type 2 Diabetes Mellitus

Circulation ◽

10.1161/circ.116.suppl_16.ii_825-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Massimo Salvetti ◽

Maria Lorenza Muiesan ◽

Barbara Stanga ◽

Antonio Cimino ◽

Umberto Valentini ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Total Cholesterol ◽

Odds Ratio ◽

Cardiovascular Events ◽

Prognostic Significance ◽

Type 2 Dm ◽

Increased Risk

Background: A large number of studies have demonstrated that LVH detected with standard electrocardiography is an independent predictor of future cardiovascular complications in various subsets of patients. Despite the fact that ECG represents the first cardiovascular test performed in diabetics, few data are available on the prognostic significance of EKG LVH in these patients. Aim of this study was to evaluate the relationship between EKG LVH and the risk of future cardiovascular events in a wide group of patients with diabetes mellitus (DM). Methods A total of 1131 prospectively identified patients with type 1 (n=613, age 36 ± 13 years, 40 % women, BP 127 ± 16/79 ± 8 mmHg, total cholesterol 196 ± 43 mg/dl, HbA1C 7.81 ± 1.67%) and with type 2 DM (n=618, age 53 ± 11 years, 34 % women, BP 137 ± 18/82 ± 8 mmHg, total cholesterol 208 ± 41 mg/dl, HbA1C 7.97 ± 1.72%) were studied. At baseline all subjects underwent baseline clinical examination with blood pressure measurement according to current guidelines, standard laboratory examinations and a 12 leads electrocardiogram. LVH was defined as the presence of a “Sokolow-Lyon” voltage >38 mm and/or a “Cornell voltage QRS duration product” >2440 mm* msec. Treatment was not standardized. Results LVH prevalence was 8.3 % in type 2 DM and 6.4 % in type 1 DM. Patients were followed for 63 ± 27 months (range 1–126). A first non fatal cardiovascular event occurred in 62 patients. Kaplan-Meyer analysis revealed a higher risk of cardiovascular events in patients with LVH both with type 1 and type 2 DM (Log Rank Mantel Cox p<0.01). In Cox analysis, controlling for age, gender, BMI, history of cardiovascular disease, systolic blood pressure, heart rate, total plasma cholesterol, HbA1c, albuminuria and antihypertensive treatment, the presence of LVH was associated with an increased risk of cardiovascular events in all patients (odds ratio 2.96, 95% CI 1.39 to 6.32, p<0.01) and separately in DM type 1 (odds ratio 5.71, 95% CI 1.29 to 25.17, p=0.02) and in type 2 DM (odds ratio 2.92, 95% CI 1.02 to 8.35, p=0.05). Conclusions: Our data demonstrate that in patients with DM the detection of LVH by EKG is associated to an increased risk of cardiovascular events, independently of other risk factors and represent the first demonstration of the prognostic significance of EKG-LVH in patients with type 1 diabetes

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