Inhibitors of cyclooxygenase augment serotonergic responsiveness in canine coronary arteries.
Experiments were designed to determine the role of products of cyclooxygenase in contractions of coronary smooth muscle evoked by serotonin. Rings of canine coronary artery without endothelium were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Serotonin caused concentration-dependent contractions followed by secondary relaxations at higher doses. Indomethacin and meclofenamate augmented both the contraction and the relaxation. Indomethacin did not affect contractions evoked by increasing concentrations of either phenylephrine, prostaglandin F2 alpha, or potassium chloride. Propranolol did not affect the concentration-response curve to serotonin under control conditions; it prevented the facilitated contraction to the monoamine but not the augmented secondary relaxation caused by the inhibitors of cyclooxygenase. These results suggest that endogenous prostanoids simultaneously inhibit the contractile process and brake relaxations induced by higher concentrations of serotonin. As a consequence, inhibitors of prostanoid formation facilitate the vasospastic component of the response to the monoamine in large coronary arteries. For unknown reasons, propranolol prevents this facilitation.
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D010656:Phenylephrine; D012701:Serotonin; D008469:Meclofenamic Acid; D011189:Potassium Chloride; D011433:Propranolol; D015237:Dinoprost; D007213:Indomethacin