Presence and mechanism of direct vascular effects of amiloride in humans

Besides an evident diuretic effect, amiloride has been shown to exert direc t vasoactivity in various animal experiments, whereas human data on this is sue are lacking. Inhibition of Na+/H+ exchange, alpha-adrenegic blockade, a nd sodium and calcium channel antagonism have been proposed as possible mec hanisms of this action. Although the role of Na+/H+ exchange in vascular-to ne modulation is not completely clear, various vasoconstrictive agents (e.g ., angiotensin II) enhance its activity. We examined the direct effects of amiloride on human arterial vasculature in vivo. Forearm vasodilator respon ses to the infusion of placebo and amiloride (n = 10; 0.1-100 mu g/min/dl) into the brachial artery were recorded by venous occlusion strain-gauge ple thysmography. Reduction of forearm blood flow after local administration of noradrenaline or angiotensin II was measured before and after local amilor ide administration. Amiloride increased the ratio of the infused/ noninfuse d forearm blood flow at the highest dosages (10, 30 and 100 mu g/min/dl wit h 14 +/- 9, 17 +/- 14, 58 +/- 23% (p = 0.002, repeated-measures analysis of variance). In contrast to noradrenaline-induced vasoconstriction, the vaso constrictor response to angiotensin II was significantly attenuated by amil oride (p = 0.02). At high concentrations, amiloride exerts direct vasodilat or activity in human arterial vasculature in vivo. This effect appears not to depend on alpha-adrenergic receptor blockade, but shows interaction with angiotensin II, an activator of Na+/H+ exchange.