Neely C F, Haile D, Matot I
Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia.
J Pharmacol Exp Ther. 1993 Mar;264(3):1315-26.
Mechanisms to explain tone-dependent responses of the feline pulmonary vascular (PV) bed to 5-hydroxytryptamine (5-HT) were investigated in intact-chest, spontaneously breathing cats under conditions of controlled pulmonary blood flow and constant left atrial pressure. At low (resting) PV tone, intralobar injections of 5-HT produced dose-dependent vasoconstrictor (VC) responses which were significantly blocked by the selective 5-HT2 receptor antagonist ketanserin and enhanced by the cyclooxygenase inhibitor meclofenamate. When PV tone was increased with 9,11-dideoxy-9 alpha 11 alpha epoxymethano prostaglandin F2 alpha, intralobar injections of 5-HT produced vasodilator (VD) responses at low doses, biphasic VC/VD responses at midrange doses and predominant VC responses at high doses. The VC responses at elevated PV tone were dose dependent and antagonized by ketanserin. The VD responses were antagonized by the mixed 5-HT1, 5-HT2 receptor antagonist methysergide. Meclofenamate had no effect on VC or VD responses of 5-HT at elevated PV tone. At both low (resting) and elevated PV tone, 5-HT and the selective 5-HT2 receptor agonist alpha-methyl-5-HT produced greater VC responses than the selective 5-HT1 receptor agonist 5-carboxyaminotryptamine and the selective 5-HT3 receptor agonist 2-methyl-5-HT. At elevated PV tone, 5-carboxyaminotryptamine and 5-HT produced greater VD responses than alpha-me-5-HT and 2-methyl-5-HT. Compared to low (resting) PV tone, VC responses of 5-HT and alpha-methyl-5-HT were enhanced at elevated PV tone. These data support that 5-HT-induced VC responses at both low (resting) and elevated PV tone are mediated by 5-HT2 receptors and 5-HT-induced VD responses at elevated PV tone are mediated by "5-HT1-like" receptors. A change in PV tone may alter receptor availability, affinity or receptor-effector coupling.
