ENDOGENOUS ANGIOTENSIN-II CONTRIBUTES TO BASAL PERIPHERAL VASCULAR TONE IN SODIUM DEPLETE BUT NOT SODIUM REPLETE MAN

Objective: Both endothelin-1 and nitric oxide make important contribut ions to the maintenance of basal peripheral arteriolar tone. However, the role of angiotensin II, a key hormone regulating cardiovascular an d renal function, in the regulation of peripheral vascular tone has no t been fully characterised. Methods: Using local intra-arterial admini stration of losartan, a selective angiotensin II type 1 (AT(1)) recept or antagonist, we examined the contribution of endogenous angiotensin II to the maintenance of basal and sympathetically stimulated vascular tone in the forearm of healthy man under conditions of sodium repleti on and depletion. The effects of losartan on responses to exogenous an giotensin I, angiotensin II, bradykinin and noradrenaline were also de termined. Results: Losartan, in keeping with its actions as a selectiv e AT(1) receptor antagonist, inhibited responses to angiotensin I and II, but had no effect on responses to bradykinin or noradrenaline. The dose of angiotensin II required to cause a 20% vasoconstriction was 4 0- and 250-fold greater with 30 and 300 mu g/min of losartan, respecti vely. However, in sodium replete subjects, losartan alone caused no si gnificant changes in basal forearm blood flow (95% confidence interval of -7.2 to +8.0%), forearm vascular resistance or sympathetically sti mulated forearm vasoconstriction. Sodium depletion elevated plasma ren in activity and angiotensin II concentrations (p less than or equal to 0.002) after which acute local administration of losartan increased f orearm blood flow in a dose dependent manner (maximum of 69 +/- 17%; p < 0.001). Conclusions: Endogenous angiotensin II does not contribute to the acute local maintenance of basal peripheral vascular tone in he althy man except under conditions of renin-angiotensin system activati on such as sodium depletion. (C) 1997 Elsevier Science B.V.