Bindu Chamarthi1, Jonathan S Williams, Gordon H Williams. 1. Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's and Harvard Medical School, Boston, Massachusetts 02115, USA. bchamarthi@partners.org
Abstract
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 (ANGII) might also exist in salt-sensitive hypertension because of the interplay of the renin-angiotensin system and dietary sodium. METHODS: Blood pressure (BP) response to ANGII infusion was studied in 295 hypertensive and 165 normotensive individuals after 7 days of high (200 mEq/day) and low (10 mEq/day) dietary sodium. RESULTS: Normotensive individuals demonstrated higher BP response to ANGII on high-salt than low-salt diet, whereas hypertensive individuals had similar responses on both diets; that is, the high-salt response was not enhanced as compared with low-salt response. Additionally, hypertensive individuals had a significantly greater high-salt BP response to norepinephrine than to ANGII. There was no correlation between the high-salt hormone levels and the difference in BP response to ANGII between the two diets. When stratified by BP response to dietary salt restriction, individuals with salt sensitivity of BP demonstrated abnormal high-salt BP responsiveness to ANGII. To assess if this represented increased tissue renin-angiotensin system activity in the vasculature, BP responses to angiotensin were compared before and after captopril in 20 hypertensive individuals on a high-salt diet. Individuals with the greatest BP-lowering effect to captopril had similar high and low-salt BP responses to ANGII at baseline and a significant increase in the high-salt response after captopril. CONCLUSION: Hypertensive individuals have an abnormal vascular response to ANGII 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.
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 (ANGII) might also exist in salt-sensitive hypertension because of the interplay of the renin-angiotensin system and dietary sodium. METHODS: Blood pressure (BP) response to ANGII infusion was studied in 295 hypertensive and 165 normotensive individuals after 7 days of high (200 mEq/day) and low (10 mEq/day) dietary sodium. RESULTS: Normotensive individuals demonstrated higher BP response to ANGII on high-salt than low-salt diet, whereas hypertensive individuals had similar responses on both diets; that is, the high-salt response was not enhanced as compared with low-salt response. Additionally, hypertensive individuals had a significantly greater high-salt BP response to norepinephrine than to ANGII. There was no correlation between the high-salt hormone levels and the difference in BP response to ANGII between the two diets. When stratified by BP response to dietary salt restriction, individuals with salt sensitivity of BP demonstrated abnormal high-salt BP responsiveness to ANGII. To assess if this represented increased tissue renin-angiotensin system activity in the vasculature, BP responses to angiotensin were compared before and after captopril in 20 hypertensive individuals on a high-salt diet. Individuals with the greatest BP-lowering effect to captopril had similar high and low-salt BP responses to ANGII at baseline and a significant increase in the high-salt response after captopril. CONCLUSION:Hypertensive individuals have an abnormal vascular response to ANGII 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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