Effects of sodium depletion on the role of AT1- and alpha-adrenergic receptors in the regulation of forearm vascular tone in humans.

Abstract

Sodium depletion stimulates the renin-angiotensin and sympathetic nervous systems, which may affect the role of each of these systems in the regulation of vascular tone. We investigated the influence of sodium depletion on the roles of the angiotensin II type 1 receptor and the alpha1- and alpha2-adrenergic receptors, and on nitric oxide generation, in the regulation of human forearm vascular tone. We studied the effects of the angiotensin II type 1 receptor antagonist losartan (0.1-3 microg/kg per min), angiotensin II (0.01-10 ng/kg per min), the alpha1- and alpha2-adrenoceptor antagonists doxazosin (3-100 ng/kg per min) and yohimbine (0.5-4 microg/kg per min) and the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 7.5-60 microg/kg per min) on forearm blood flow in control subjects (n = 12) and sodium-depleted subjects (n = 11). Sodium depletion was achieved by 3 days of pretreatment with 40 mg furosemide twice a day and a sodium-restricted diet. Forearm blood flow was measured by venous occlusion plethysmography. Sodium depletion resulted in activation of the renin-angiotensin and sympathetic nervous systems, as indicated by increased levels of plasma renin, aldosterone and heart rate (P < 0.05). Blood pressure remained unchanged. Losartan at the highest dose increased forearm blood flow in the sodium-depleted group by 42 +/- 9%, but had no effect in controls (P < 0.05). Both doxazosin and yohimbine caused an increased vasodilatory effect in the sodium-depleted versus the control group (228 +/- 42 versus 83 +/- 13% and 192 +/- 24 versus 95 +/- 8%, respectively; P < 0.05). The constrictor effects by angiotensin II and L-NMMA of -65 +/- 6% and -79 +/- 4%, respectively, in controls were unchanged by sodium depletion. In sodium-depleted subjects, endogenous angiotensin II appears to play a role in the regulation of forearm vascular tone, in contrast to sodium-replete conditions. Furthermore, in these subjects the role of alpha1- and alpha2-adrenoceptors in the regulation of forearm vascular tone was enhanced compared with control conditions. Neither the forearm vascular effects of exogenously infused angiotensin II nor those of baseline nitric oxide production were influenced by sodium depletion.