Tone-dependent responses of 5-hydroxytryptamine in the feline pulmonary vascular bed are mediated by two different 5-hydroxytryptamine receptors

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-9α11α epoxymethano prostaglandin F(2α), 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 VC 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 α-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 α-me- 5-HT and 2-methyl-5-HT. Compared to low (resting) PV tone, VC responses of 5- HT and α-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.