Alpha 1-adrenoceptor-blocking activity of ofloxacin and ciprofloxacin in isolated vascular smooth muscles.
Using vascular strips from dogs and rabbits, we investigated whether the hypotensive action of ofloxacin enantiomers could be ascribed to effects on vascular smooth muscle. (+)-Ofloxacin, (-)-ofloxacin, (+/-)-ofloxacin and ciprofloxacin competitively inhibited contractions induced by norepinephrine or phenylephrine in dog mesenteric artery and rabbit aortic smooth muscles, without affecting the maximum contractions, whereas they did not affect contractions induced by high KCl. (-)-Ofloxacin did not affect the contractions induced by prostaglandin F2 alpha, 5-hydroxy-tryptamine, U46619 and angiotensin II. Pretreatment with (-)-ofloxacin protected alpha 1-receptors of rabbit aortas from the irreversible blockade by phenoxybenzamine. Any action on the vascular endothelium or intracellular Ca release was not involved in the vasorelaxing action of the drugs. The results suggest that these drugs have an antagonistic action on alpha 1-adrenoceptors in vascular smooth muscles and that this action is, at least partly, responsible for the hypotensive action.
Ito
K
K
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan.
Murakami
K
K
Tamura
K
K
D000818:Animals; D002939:Ciprofloxacin / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D018340:Receptors, Adrenergic, alpha-1; D010643:Phenoxybenzamine; D002939:Ciprofloxacin; D011189:Potassium Chloride; D015242:Ofloxacin; D015237:Dinoprost; D009638:Norepinephrine