Prostanoid mediation of pulmonary vascular response to acetylcholine in rabbits.
We studied the effects of acetylcholine (ACh) in the anesthetized, open-chest rabbit. ACh (5-20 nmol/kg), administered as a bolus into the right jugular vein, produced a dose-dependent increase in both pulmonary arterial pressure and pulmonary vascular resistance but a decrease in systemic arterial pressure and pulmonary blood flow. All these effects were prevented by atropine. Pretreatment with the phospholipase A2 inhibitor quinacrine reduced the pulmonary vascular responses to ACh without affecting systemic arterial pressure. Similarly, treatment with the cyclooxygenase inhibitors indomethacin or meclofenamate completely eliminated the pulmonary vascular response to ACh without affecting systemic arterial pressure or pulmonary blood flow. Treatment with the lipoxygenase inhibitor nordihydroguaiaretic acid, however, had no effect on the pulmonary or systemic vascular responses to ACh. Furthermore, administration of the thromboxane A2 synthetase inhibitor 7-(1-imidazolyl)-heptanoic acid or the thromboxane A2 receptor antagonist SQ 29,548 completely eliminated the pulmonary vascular responses to ACh without affecting systemic arterial pressure or pulmonary blood flow. Plasma levels of immunoreactive thromboxane B2 increased after ACh, in the absence but not in the presence of the thromboxane A2 synthetase inhibitor. The results of the present study indicate that in the rabbit ACh has opposite actions in the systemic (dilatory) versus pulmonary (constrictor) circulation, arachidonic acid metabolites mediate the pulmonary but not the systemic vascular response to ACh, and thromboxane A2 appears to mediate the pulmonary vasoconstrictor response to ACh.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology
D011453:Prostaglandins; D013928:Thromboxane A2; D009637:Masoprocol; D011796:Quinacrine; D000109:Acetylcholine