Mechanisms of methyclothiazide-induced inhibition of contractile responsesin rat aorta

Methyclothiazide (MCTZ), a thiazide diuretic, inhibits the contractile resp onse induced by norepinephrine in aortic rings from 12-week-old spontaneous ly hypertensive rats (SHR). Although not modified by indomethacin, this inh ibition was attenuated by either mechanical removal of the endothelium or N omega -nitro-L-arginine (NOLA) treatment. These results suggest that the M CTZ effects on the norepinephrine-evoked vascular response are mediated by an endothelium-dependent mechanism involving endothelium-dependent relaxing factor (EDRF)/nitric oxide (NO) release. MCTZ was also found to alter the contractile response induced by the addition of Ca2+ to a depolarizing solu tion, and this inhibitory effect was partially abolished by NOLA applicatio n. Our data led us to propose that MCTZ relaxes aortic rings, resulting in an endothelium-dependent relaxation phenomenon that could even be reinforce d under high-K+ depolarizing conditions. (C) 2000 Elsevier Science B.V. All rights reserved.