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 (1×10-5, 3×10-5 and 1×10-4 M for coronary artery; 3×10-5 and 1×10-4 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 (1×10-4 M), and the inhibition was reversed dose-dependently by addition of CaCl2. Flurazepam and diazepam (3×10-5 and 1×10-4 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.