Effect of hypoxia on the contractile response to KCl, prostaglandin F2 alpha, and hemoglobin.
The purpose of this experiment was to evaluate the effect of hypoxia on the in vitro contractile responses of canine basilar artery to KCl, prostaglandin (PG) F2 alpha, and hemoglobin. Hypoxia was induced by changing the bubbling gas mixture in the chamber from 95% O2/5% CO2 to 95% N2/5% CO2. Hypoxia augmented the contractile response developed at 95% O2 to 25 mM and 50 mM KCl, 3 X 10(-7) M and 10(-5) M PGF2 alpha, and 10(-6) M hemoglobin. No significant alteration of the hypoxic augmentation in any preparation exposed to 25 mM KCl, 3 X 10(-7) M PGF2 alpha, or 10(-6) M hemoglobin was observed with guanethidine (10(-5) M), prazosin (10(-5) M), methysergide (10(-5) M), or diphenhydramine (10(-5) M). Endothelial denudation did not affect hypoxic augmentation. Hypoxia did not cause any alteration of the contractile response to 10(-6) M PGF2 alpha in Ca++-free media. Pretreatment with a calcium channel blocker, nicardipine, significantly inhibited the hypoxic potentiation of the contractile response to 25 mM KCl, 3 X 10(-7) M PGF2 alpha, and 10(-6) M hemoglobin. These results suggest that hypoxia augments the contractile response to these agonists by a direct action on the smooth-muscle cells, facilitating the transmembrane influx of extracellular calcium. Hypoxia of smooth-muscle cells in the major cerebral arteries might be involved in the pathogenesis of vasospasm.
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000502:physiology; D015237:Dinoprost; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006454:Hemoglobins / Q000502:physiology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology*
D006454:Hemoglobins; D011460:Prostaglandins F; D011189:Potassium Chloride; D015237:Dinoprost; D009529:Nicardipine; D002118:Calcium