5-hydroxytryptamine receptors mediating vasoconstriction and vasodilation in perinatal and adult rabbit small pulmonary arteries.

Abstract

1. Vasoconstrictor responses to 5-HT, 5-carboxamidotryptamine (5-CT, 5-HT1 receptor agonist), alpha-methyl-5-HT (5-HT2 receptor agonist) and sumatriptan (5-HT1D/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 Nomega-nitro-L-arginine methylester (L-NAME). The effect of the selective 5-HT receptor antagonists ketanserin (5-HT2A receptor) and GR55562 (5-HT1B/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 alpha-methyl-5-HT were equipotent in causing contraction in the PRAs at each age (e.g. pEC50s for 5-HT and alpha-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 pEC50s 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 nM and 0.1 microM) but not GR55562 (1 microM). 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-HT7 receptor antagonist spiperone (1 microM). 8. The results suggest that 5-HT2A-receptors mediate vasoconstriction in perinatal vessels whilst the 5-HT1D or 5-HT1B receptor contributes in adult rabbit vessels. The 5-HT1D or 5-HT1B receptor mediates NO-dependent vasodilation in vessels from rabbits at 4 days of age whilst 5-HT7 receptors mediate NO-independent vasodilation by 7 days.