Analysis of responses to serotonin in the pulmonary vascular bed of the cat.
Pulmonary vascular responses to serotonin (5-hydroxytryptamine; 5-HT) were investigated in the intact-chest cat under constant-flow conditions. Injections of 5-HT into the perfused lobar artery in doses of 1-30 micrograms caused dose-related increases in lobar arterial pressure and, at doses of 3-30 micrograms, decreases in systemic arterial pressure. Left atrial pressure was not changed, and responses to 5-HT were not altered by a thromboxane receptor blocking agent. Responses to 5-HT were blocked by ketanserin in doses that did not alter responses to agonists that increase pulmonary vascular resistance by various mechanisms. The ketanserin-induced blockade was not surmountable and at a dose of 0.5 mg/kg iv persisted for > 4 h. Prazosin and yohimbine, selective alpha 1- and alpha 2-adrenoceptor antagonists, were without effect on the pressor response to 5-HT, and ketanserin did not reduce responses to norepinephrine or the alpha 1-agonists, phenylephrine and methoxamine. 5-HT and the thromboxane mimic, U-46619, produced large increases in pulmonary vascular resistance; however, U-46619 was 300 times more potent than 5-HT. 5-HT increased lobar arterial pressure when the lung was perfused with dextran, and increases in lobar arterial pressure in response to 5-HT were not diminished when lobar ventilation was interrupted but were enhanced by N omega-nitro-L-arginine methyl ester and to a small extent by meclofenamate. The present data suggest that increases in pulmonary vascular resistance in the cat in response to 5-HT are due to activation of an S2 receptor in undefined "resistance vessel elements." These data suggest that pulmonary vasoconstrictor responses to 5-HT may be modulated to a small extent by release of a vasodilator prostaglandin and endothelium-derived nitric oxide but are not dependent on activation of thromboxane receptors, changes in bronchomotor tone, and interaction with alpha 1-receptors or with formed elements in blood.
McMahon
T J
TJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Hood
J S
JS
Nossaman
B D
BD
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D002415:Cats; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D005473:Fluoxetine; C054215:SQ 30741; D012701:Serotonin; D008469:Meclofenamic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D007650:Ketanserin; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine