ON THE EXISTENCE OF FUNCTIONAL ANGIOTENSIN-II RECEPTORS ON VASCULAR SYMPATHETIC-NERVE TERMINALS IN THE HUMAN FOREARM

Objective: The existence of presynaptic angiotensin II receptors, modu lating the release of the sympathetic neurotransmitter norepinephrine, was examined in the perfused human forearm model. Design and methods: In three groups out of a total of 20 healthy volunteers, intra-arteri al infusions of tracer amounts of tritiated norepinephrine were given to measure forearm spillover and total plasma appearance rate of norep inephrine during intra-arterial infusions of angiotensin II (0.02, 0.2 acid 2 ng/kg per min), methoxamine (0.08, 0.4 and 2 mu g/kg per min) to produce vasoconstriction by stimulating alpha 1-adrenoceptors and s aralasin (0.5 ng/kg per min) to block angiotensin II receptors. Postga nglionic sympathoneural activity was stimulated by intravenous infusio n of sodium nitroprusside (about 1.3 ng/kg per min) or attenuated by i ntravenous infusion of trimethaphan (about 1 mg/min).Results: Angioten sin II failed to increase the spillover and total plasma appearance ra te of norepinephrine, when given without additional treatment or durin g sodium nitroprusside or trimethaphan administration. In contrast, th e spillover of norepinephrine even decreased during angiotensin II adm inistration, both before and during intravenous sodium nitroprusside a dministration, probably because of angiotensin II-induced forearm vaso constriction. Similar vasoconstrictor doses of angiotensin II and meth oxamine produced similar changes in spillover and total plasma appeara nce rate of norepinephrine. The highest dose of angiotensin II increas ed diastolic blood pressure by 9% and decreased the pulse rate by 6%. Saralasin affected the spillover and total plasma appearance rate of n orepinephrine neither before nor during intravenous sodium nitroprussi de infusion. Conclusion: The present results fail to support the view that angiotensin II receptors exert stimulatory modulatory effects on norepinephrine release from sympathetic nerves in the human forearm, a t rest or during changes in sympathoneural outflow.