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- 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), a lone and in the presence of the NO synthase inhibitor N-omega-nitro-L- arginine methylester (L-NAME). The effect of the selective 5-HT recept or antagonists ketanserin (5-HT2A receptor) and GR55562 (5-HT1B/1D rec eptor) on vasoconstrictor responses to 5-HT were studied in the presen ce of L-NAME. Vasodilator responses to 5-CT were also studied in pre-c ontracted PRAs. 3 5-HT and alpha-methyl-5-MT were equipotent in causin g contraction in the PRAs at each age (e.g. pEC(50)s for 5-HT and alph a-methyl-5-MT were 6.74 +/- 0.13 and 6.63 +/- 0.22 respectively in adu lt vessels). In the perinatal PRAs, sumatriptan and 5-CT produced negl igible contractions, but in adult PRAs, 5-CT and sumatriptan were pote nt agonists with pEC(50)s Of 6.05 +/- 0.3 and 5.70 +/- 0.20 respective ly. 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 mu M) but not GR55562 (1 mu M). A small ketanserin-resistant, GR55 562-sensitive component was observed at 0-24 h. In adult vessels, both ketanserin and GR55562 inhibited 5-HT-induced responses. 7 Vasodilato r 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 vess els. At 4 days the vasodilator response was inhibited both by L-NAME a nd GR55562. At 7 days the response was only partly blocked by L-NAME a nd resistant to GR55562. The L-NAME resistant component was antagonize d by the 5-HT7 receptor antagonist spiperone (1 mu M). 8 The results s uggest that 5-HT2A-receptors mediate vasoconstriction in perinatal ves sels whilst the 5-HT1D or 5-HT1B receptor contributes in adult rabbit vessels. The 5-HT1D or 5-HT1B receptor mediates NO-dependent vasodilat ion in vessels from rabbits at 4 days of age whilst 5-HT7 receptors me diate NO-independent vasodilation by 7 days.