ANGIOTENSIN AT(1) RECEPTOR BLOCKADE ABOLISHES THE REFLEX SYMPATHOEXCITATORY RESPONSE TO ADENOSINE

We tested the hypothesis that endogenous angiotensin II participates i n the direct and reflex effects of adenosine on the sympathetic nervou s system, Nine healthy men were studied after 1 wk of the angiotensin II type I receptor antagonist losartan (100 mg daily) or placebo, acco rding to a double-blind randomized crossover design, Bilateral forearm blood flows, NE appearance rates, and total body NE spillover were de termined before and during graded brachial arterial infusion of adenos ine (0.5, 1.5, 5, and 15 mu g/100 ml forearm tissue) and nitroprusside . Adenosine increased total body NE spillover (P < 0.05) whereas nitro prusside did not. Losartan lowered BP (P < 0.05), had no effect on tot al body NE spillover at rest, or forearm vasodilation during either in fusion, but reduced the systemic noradrenergic response to adenosine f rom 1.0+/-0.4 nmol/min on the placebo day to 0.2+/-0.3 nmol/min (P < 0 .01), and forearm NE appearance rate in response to adenosine was lowe r in the infused, as compared with the contralateral arm (P = 0.04), T he sympatho-excitatory reflex elicited by adenosine is mediated throug h pathways involving the angiotensin II type I receptor, Interactions between adenosine and angiotensin II may assume importance during isch emia or congestive heart failure and could contribute to the benefit o f converting enzyme inhibition in these conditions.