5‐Hydroxytryptamine receptors mediating vasoconstriction and vasodilation in perinatal and adult rabbit small pulmonary arteries

1 Vasoconstrictor responses to 5‐HT, 5‐carboxamidotryptamine (5‐CT, 5‐HT 1 receptor agonist), α‐methyl‐5‐HT (5‐HT 2 receptor agonist) and sumatriptan (5‐HT 1D/1B receptor agonist) were studied in fetal, 0–24 h, 4 day, 7 day and adult rabbit pulmonary resistance arteries (PRAs), alone and in the presence of the NO synthase inhibitor N ω ‐nitro‐ L ‐arginine methylester ( L ‐NAME). The effect of the selective 5‐HT receptor antagonists ketanserin (5‐HT 2A receptor) and GR55562 (5‐HT 1B/1D receptor) on vasoconstrictor responses to 5‐HT were studied in the presence of L ‐NAME. Vasodilator responses to 5‐CT were also studied in pre‐contracted PRAs. 3 5‐HT and α‐methyl‐5‐HT were equipotent in causing contraction in the PRAs at each age (e.g. p EC 50 s for 5‐HT and α‐methyl‐5‐HT were 6.74±0.13 and 6.63±0.22 respectively in adult vessels). In the perinatal PRAs, sumatriptan and 5‐CT produced negligible contractions, but in adult PRAs, 5‐CT and sumatriptan were potent agonists with p EC 50 s of 6.05±0.3 and 5.70±0.20 respectively. 4 L ‐NAME markedly increased the maximum response to 5‐HT in the 0–24 h, 4 day and 7 day vessels and increased 5‐HT potency in the 4‐, 7‐day‐old and adult rabbit vessels. 5 In perinatal vessels, responses to 5‐HT, with L ‐NAME present, were antagonized by ketanserin (30 n M and 0.1 μ M ) but not GR55562 (1 μ M ). A small ketanserin‐resistant, GR55562‐sensitive component was observed at 0–24 h. In adult vessels, both ketanserin and GR55562 inhibited 5‐HT‐induced responses. 7 Vasodilator responses to 5‐CT were observed in pre‐contracted PRAs from 4‐ and 7‐day‐old rabbits but not in the fetus, 0–24 h old or adult rabbit vessels. At 4 days the vasodilator response was inhibited both by L ‐NAME and GR55562. At 7 days the response was only partly blocked by L ‐NAME and resistant to GR55562. The L ‐NAME resistant component was antagonized by the 5‐HT 7 receptor antagonist spiperone (1 μ M ). 8 The results suggest that 5‐HT 2A ‐receptors mediate vasoconstriction in perinatal vessels whilst the 5‐HT 1D or 5‐HT 1B receptor contributes in adult rabbit vessels. The 5‐HT 1D or 5‐HT 1B receptor mediates NO‐dependent vasodilation in vessels from rabbits at 4 days of age whilst 5‐HT 7 receptors mediate NO‐independent vasodilation by 7 days.British Journal of Pharmacology (1998) 125 , 69–78; doi: 10.1038/sj.bjp.0702055