Effects of BRL 34915, a putative K channel opener, on transmembrane 45Ca movements in rabbit aortic smooth muscle.

The effects of BRL 34915, a putative K channel opener, on transmembrane Ca2+ movements were studied in isolated rabbit aortic strips, using the 45Ca flux techniques. BRL 34915 (1 and 10 microM) inhibited the contraction and Ca entry in response to norepinephrine (NE) and angiotensin II, each at 0.3 microM. BRL 34915 differed from Na nitroprusside in that it demonstrated little or no inhibition on the contraction and 45Ca efflux provoked by NE in Ca2+-free buffer, suggesting that the effect of BRL 34915 on intracellular Ca release plays a minor role in inhibiting the vasoconstrictor responses to receptor agonists. Moreover, BRL 34915 (100 microM) did not stimulate cyclic GMP formation in rabbit aortic slices. BRL 34915 (10 microM) failed to inhibit the vascular responses to KCl (20 and 40 mM). Tetraethylammonium (20 mM), a K channel blocker, abolished the vasorelaxant action of BRL 34915 against NE. However, Na nitroprusside inhibition of NE contraction was similarly affected. It is concluded that reduction of Ca entry appears to be the predominant mechanism mediating the inhibitory effect of BRL 34915 on the contractile responses to vasoconstrictor stimuli.