[Effect of methyclothiazide on the entry of calcium into vascular smooth muscle cells].
The possible involvement of calcium and potassium channels in mediating the vascular actions of methyclothiazide (MCTZ), a thiazide diuretic, was investigated in isolated aortic rings from 12 week-old hypertensive rats. MCTZ (10(-4) M) inhibits the contractile response induced by addition of Ca2+ to a depolarizing solution, the maximal contracture is reduced by 87.16 +/- 6.4%. Furthermore this inhibitory effect was unaffected by charybdotoxine a selective blocker of calcium-activated K+ channels (Kca). This suggesting that MCTZ inhibits voltage-gated Ca2+ channels and blunts the Ca2+ entry into vascular smooth muscle cells. This inhibition was partially attenuated by either mechanical removal of the endothelium or N omega-nitro-L-arginine (NOLA) treatment, suggesting that MCTZ effects are also mediated by an endothelium-dependent mechanism involving endothelium-dependent relaxing factor (EDRF)/nitric oxide (NO) release. Taken together, these observations could point to a role of voltage-gated Ca2+ channels and endothelial release of EDRF/NO in the antihypertensive action of MCTZ.
Colas
B
B
Colas
J L
JL
Masson
H
H
Slama
M
M
Collin
T
T
Andrejak
M
M
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D004232:Diuretics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008736:Methyclothiazide / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004232:Diuretics; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D049993:Sodium Chloride Symporter Inhibitors; D014665:Vasodilator Agents; D018999:Charybdotoxin; D019335:Nitroarginine; D009569:Nitric Oxide; D008736:Methyclothiazide; D002118:Calcium