The pharmacological basis of coronary and systemic vasodilator actions of diazepam (Valium).
1. The effects of alpha and beta-adrenoceptor blockade, depletion of catecholamine stores, vagotomy, atropine, and ganglionic blockade on diazepam-induced vasodilatation were investigated in forty-six anaesthetized dogs.2. Coronary blood flow was measured by timed collections of coronary venous efflux from fibrillating, decompressed ventricles; coronary and systemic vascular resistances were determined during total cardiopulmonary bypass under conditions of normothermia and constant aortic (coronary artery) pressure.3. No significant alteration in the vasodilatation produced by diazepam was observed following either vagotomy or alpha-adrenoceptor blockade; partial inhibition of vasodilatation occurred after beta-adrenoceptor blockade or catecholamine depletion, and nearly total inhibition was observed after small doses of atropine or ganglion-blocking agents.4. The results suggest that diazepam may act as a specific ganglion-stimulant, causing active sympathetic and cholinergic vasodilatation.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004285:Dogs; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D014294:Trimethaphan / Q000494:pharmacology; D014628:Vagotomy; D014655:Vascular Resistance / Q000187:drug effects*
D010643:Phenoxybenzamine; D014294:Trimethaphan; D001285:Atropine; D012110:Reserpine; D011433:Propranolol; D003975:Diazepam