Altered Adrenal Sensitivity to Angiotensin II in Low-Renin Essential Hypertension

Fisher, Naomi D.L.; Hurwitz, Shelley; Ferri, Claudio; Jeunemaı̂tre, Xavier; Hollenberg, Norman K.; Williams, Gordon H.

doi:10.1161/01.hyp.34.3.388

Cited by 56 publications

(27 citation statements)

References 29 publications

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“…All subjects gave written informed consent before enrollment and underwent identical protocols at each study site. Some characteristics of subsets of this population have been reported previously [10, 11, 20]. However, the present analyses are original.…”

Section: Methodsmentioning

confidence: 73%

A mechanism for salt-sensitive hypertension: abnormal dietary sodium-mediated vascular response to angiotensin-II

Chamarthi¹,

Williams²,

Williams³

2010

Journal of Hypertension

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Objectives Several mechanisms have been proposed for salt-sensitive hypertension with most focusing on impaired renal sodium handling. We tested the hypothesis that abnormalities in peripheral vascular responsiveness to angiotensin-II might also exist in salt-sensitive hypertension because of the interplay of the renin-angiotensin system and dietary sodium. Methods Blood pressure response to angiotensin-II infusion was studied in 295 hypertensives and 165 normotensives after 7 days of high (200 mEq/day) and low (10 mEq/day) dietary sodium. Results Normotensives demonstrated higher blood pressure response to angiotensin-II on high-salt than low-salt diet whereas hypertensives had similar responses on both diets, i.e., the high-salt response was not enhanced compared to low-salt. Additionally, hypertensives had a significantly greater high-salt blood pressure response to norepinephrine than to angiotensin-II. There was no correlation between the high-salt hormone levels and the difference in blood pressure response to angiotensin-II between the two diets. When stratified by blood pressure response to dietary salt restriction, individuals with salt sensitivity of blood pressure demonstrated abnormal high-salt blood pressure responsiveness to angiotensin-II. To assess if this represented increased tissue renin-angiotensin system activity in the vasculature, blood pressure responses to angiotensin were compared before and after captopril in 20 hypertensives on a high-salt diet. Subjects with the greatest blood pressure lowering effect to captopril had similar high and low-salt blood pressure responses to angiotensin-II at baseline and a significant increase in the high-salt response after captopril. Conclusion Hypertensives have an abnormal vascular response to angiotensin-II infusion on a high-salt diet. Dysregulated tissue renin-angiotensin system activity may play a role in this abnormal response. These findings raise an intriguing novel possibility for the pathophysiologic mechanism of salt-sensitive hypertension.

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Section: Methodsmentioning

confidence: 73%

A mechanism for salt-sensitive hypertension: abnormal dietary sodium-mediated vascular response to angiotensin-II

Chamarthi¹,

Williams²,

Williams³

2010

Journal of Hypertension

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“…However, data regarding the role of aldosterone in low-renin hypertension is sparse. Fisher et al [20] provide a potential mechanism for increased responsiveness to aldosterone antagonism in patients with low-renin hypertension as they demonstrated that the ratio of aldosterone to plasma renin activity was higher than in other patients, despite normal absolute values of aldosterone. However, another paper by Calhoun et al [21 ]showed no significant differences.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Hyperkalemia Risk following Hypertension Control with Aldosterone Blockade

2009

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Background: Aldosterone antagonists have proven efficacy for management of resistant hypertension and proteinuria reduction; however, they are not widely used due to risk of hyperkalemia. This study assesses the risk factors for hyperkalemia in patients with chronic kidney disease (CKD) and resistant hypertension whose blood pressure (BP) is reduced to a guideline goal. Methods: This is a two-center study conducted in university-based hypertension clinics directed by clinical hypertension specialists. Forty-six patients with resistant hypertension and stages 2 or 3 CKD (mean estimated glomerular filtration rate (eGFR) 56.5 ± 16.2 ml/min/1.73 m²) were evaluated for safety and efficacy of aldosterone blockade added to preexisting BP-lowering regimens. All patients were on three mechanistically complementary antihypertensive agents including a diuretic and a renin-angiotensin system blocker. Patients were evaluated after a median of 45 treatment days. The primary endpoint was change in systolic BP. Secondary endpoints included change in serum potassium, creatinine, eGFR, diastolic BP and tolerability. Results: The mean age of the patients studied was 64.9 ± 10.7 years, all were obese and 86% had type 2 diabetes, with 82% being African-American. Addition of aldosterone antagonism yielded a further mean reduction in systolic BP of 14.7 ± 5.1 mm Hg (p = 0.001). Females with BMI >30 and those with a baseline systolic BP >160 mm Hg were more likely to have a greater BP reduction to aldosterone antagonism. In total, 39% of the patients had a >30% decrease in eGFR when the BP goal was achieved. The mean increase in serum potassium was 0.4 mEq/l above baseline (p = 0.001), with 17.3% manifesting hyperkalemia, i.e. serum potassium >5.5 mEq/l. Predictors of hyperkalemia included a baseline eGFR of ≤45 ml/min/1.73 m² in whom serum potassium was >4.5 mEq/l on appropriately dosed diuretics. Contributing risks in this subgroup included a systolic BP reduction of >15 mm Hg associated with an eGFR fall of >30%. Conclusion: Aldosterone antagonism is effective and safe for achieving a BP goal among people with diabetic nephropathy when added to a triple antihypertensive regimen that includes a blocker of the renin-angiotensin system and an appropriately selected and dosed diuretic. Caution is advised when using aldosterone blockade for BP control in people with advanced stage 3 nephropathy with a serum potassium of >4.5 mEq/l for safety reasons.

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“…17, 19–22 . The protocols were approved by the institutional review board and all subjects signed an informed consent.…”

Section: Methodsmentioning

confidence: 99%

Effect of Low Salt Diet on Insulin Resistance in Salt-Sensitive Versus Salt-Resistant Hypertension

2014

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Accumulating evidence shows an increase in insulin resistance on salt restriction. We compared the effect of low salt diet on insulin resistance in salt sensitive versus salt resistant hypertensive subjects. We also evaluated the relationship between salt sensitivity of blood pressure and salt sensitivity of insulin resistance in a multivariate regression model. Studies were conducted after one week of high salt (200 mmol/day Na) and one week of low salt (10 mmol/day Na) diet. Salt sensitivity was defined as the fall in systolic blood pressure >15mmHg on low salt diet. The study includes 389 subjects (44% Females, 16% Blacks, BMI 28.5±4.2 Kg/m2). As expected, blood pressure was lower on low salt (129±16/78±9 mmHg) as compared to high salt diet (145±18/86±10 mmHg). Fasting plasma glucose, insulin and HOMA were higher on low salt diet (95.4±19.4 mg/dl, 10.8±7.3 mIU/L and 2.6±1.9) as compared to high salt diet (90.6±10.8 mg/dl, 9.4±5.8 mIU/L and 2.1±1.4) (p <0.0001 for all). There was no difference in HOMA between salt sensitive (N=193) versus salt resistant (N=196) subjects on either diet. Increase in HOMA on low salt diet was 0.5±1.4 in salt sensitive and 0.4±1.5 in salt resistant subjects (p=NS). On multivariate regression analysis, change in systolic blood pressure was not associated with change in HOMA after including age, BMI, sex, change in serum and urine aldosterone and cortisol into the model. We conclude that the increase in insulin resistance on low salt diet is not affected by salt sensitivity of blood pressure.

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Altered Adrenal Sensitivity to Angiotensin II in Low-Renin Essential Hypertension

Cited by 56 publications

References 29 publications

A mechanism for salt-sensitive hypertension: abnormal dietary sodium-mediated vascular response to angiotensin-II

A mechanism for salt-sensitive hypertension: abnormal dietary sodium-mediated vascular response to angiotensin-II

Predictors of Hyperkalemia Risk following Hypertension Control with Aldosterone Blockade

Effect of Low Salt Diet on Insulin Resistance in Salt-Sensitive Versus Salt-Resistant Hypertension

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