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

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.

Figures

Fig. 1

SBP response to ANGII on HS versus LS diet in HTve and NTve subjects. Each subject received ANGII infusion on both HS and LS diet. Error bars represent standard error of the mean.

Fig. 2

Comparison of SBP response to NE (60ug/kg/min) and ANGII (3ng/kg/min) infusions in the same HTve subjects. Error bars represent standard error of the mean.

Fig. 3

SBP response to ANGII infusion on HS versus LS diet in the same HTve and NTve subjects stratified by salt-sensitivity of BP (salt sensitive and salt resistant). Error bars represent standard error of the mean.

Fig. 4

SBP response to ANGII and NE infusions on HS diet in hypertensives classified by renin status (low-renin and normal-renin). Each subject received both infusions. Error bars represent standard error of the mean.

Fig. 5

SBP response to ANGII infusion on HS versus LS diet. Subjects are those who received captopril and are divided into those who had a minimal BP response to captopril (tertile 1) or a maximum response (tertile 3) [see text for definition of tertiles]. The results indicate the SBP responses to ANGII on HS versus LS diet in the two groups at baseline, before receiving captopril. Error bars represent standard error of the mean.

Fig. 6

SBP response to ANGII infusion on HS diet before and after captopril (25mg) administration in HTves who had the greatest SBP response to captopril at baseline (tertile 3 individuals). These results suggest that tertile 3 subjects have higher tissue ANGII activity on a HS diet. Error bars represent standard error of the mean.