Mechanisms of methyclothiazide-induced inhibition of contractile responses in rat aorta.
Methyclothiazide (MCTZ), a thiazide diuretic, inhibits the contractile response induced by norepinephrine in aortic rings from 12-week-old spontaneously hypertensive rats (SHR). Although not modified by indomethacin, this inhibition was attenuated by either mechanical removal of the endothelium or N omega-nitro-L-arginine (NOLA) treatment. These results suggest that the MCTZ 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 Ca(2+) to a depolarizing solution, and this inhibitory effect was partially abolished by NOLA application. Our data led us to propose that MCTZ relaxes aortic rings, resulting in an endothelium-dependent relaxation phenomenon that could even be reinforced under high-K(+) depolarizing conditions.
Colas
B
B
Laboratoire de Pharmacologie et Physiopathologie Cardiovasculaire, Faculté de Médecine, Amiens, France.
Slama
M
M
Collin
T
T
Safar
M
M
Andrejak
M
M
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D015220:Calcium Channels / Q000187:drug effects; D004232:Diuretics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008736:Methyclothiazide / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*
D015220:Calcium Channels; D004232:Diuretics; D004791:Enzyme Inhibitors; D049993:Sodium Chloride Symporter Inhibitors; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D008736:Methyclothiazide