I. Morecroft et Mr. Maclean, 5-HYDROXYTRYPTAMINE RECEPTORS MEDIATING VASOCONSTRICTION AND VASODILATION IN PERINATAL AND ADULT-RABBIT SMALL PULMONARY-ARTERIES, British Journal of Pharmacology, 125(1), 1998, pp. 69-78
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.