Pharmacological effects of flurazepam and diazepam on isolated canine arteries.
The effects of flurazepam and diazepam, benzodiazepine derivatives, on contractions (or contractures) induced by Ca++, K+ or norepinephrine were examined in the isolated canine coronary artery and thoracic aorta. Ca++-Induced contraction was evoked by cumulative addition of CaCl2 to Ca++-depleted K+-depolarizing solution; K+: and norepinephrine-induced contractions were evoked by cumulative addition of KCl and norepinephrine, respectively, to the medium. Flurazepam and diazepam (1 X 10(-5), 3 X 10(-5) and 1 X 10(-4) M for coronary artery; 3 X 10(-5) and 1 X 10(-4) M for thoracic aorta) shifted the dose-response curves for KCl downwards in a non-competitive manner, and shifted the dose-response curves for CaCl2 to the right in a competitive manner. Ca++-Induced contracture was inhibited completely by addition of flurazepam or diazepam (1 X 10(-4) M), and the inhibition was reversed dose-dependently by addition of CaCl2. Flurazepam and diazepam (3 X 10(-5) and 1 X 10(-4) M) shifted the dose-response curves for norepinephrine both rightwards and downwards in the thoracic aorta. These findings suggest that flurazepam and diazepam inhibit Ca++-influx into the cells (Ca++-antagonistic effect), causing relaxation and inhibition of K+-, Ca++-, or norepinephrine-induced contraction (or contracture) of the vascular smooth muscle.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005479:Flurazepam / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology
D005479:Flurazepam; D003975:Diazepam; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine