An endothelial 5‐HT receptor that mediates relaxation in guinea‐pig isolated jugular vein resembles the 5‐HT 1D subtype

1 Vasoconstrictor responses to 5-HT, 5-carboxamidotryptamine (5-CT, 5-HT 1 receptor agonist), amethyl-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 o -nitro-L-arginine methylester (L-NAME). The e ect 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 a-methyl-5-HT were equipotent in causing contraction in the PRAs at each age (e.g. pEC 50 s for 5-HT and a-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 pEC 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 nM and 0.1 mM) but not GR55562 (1 mM). A small ketanserin-resistant, GR55562-sensitive component was observed at 0 ± 24 h. In adult vessels, both ketanserin and GR55562 inhibited 5-HTinduced 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 mM). 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 NOindependent vasodilation by 7 days.

Section: -Ht Receptor-induced Vasodilationsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 98%

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

Morecroft

MacLean

1998

“…Whilst some have been classified as 5-HT,-like (Schoeffter & Hoyer, 1990;Gupta, 1992), others may be tentatively classified as subtypes of the 5-HT2 receptor family. Thus, endothelial 5-HT receptors mediating relaxation of rabbit jugular vein (Leff et al, 1987), rat jugular vein (Bodelsson et al, 1992), piglet vena cava (Sumner, 1991) and pig pulmonary artery (Glusa, 1992) share some pharmacological identity with both 5-HT2B (Wainscott et al, 1993) and 5-HT2C (Hoyer et al, 1989) receptors.…”

Section: Introduction Methodsmentioning

confidence: 99%

Mediation by 5‐hydroxytryptamine_2B receptors of endothelium‐dependent relaxation in rat jugular vein

Ellis

Byrne

Murphy

et al. 1995

“…However, the 5-HT receptor which mediates this response is atypical and pharmacologically distinct from the vascular smooth muscle 5-HTI-like receptor subtypes Sumner, 1991). Of greater interest is the observation that both sumatriptan and 5-carboxamidotryptamine can elicit endothelial-dependent relaxation responses in the pig isolated coronary artery (Molderings et al, 1989;Schoeffter & Hoyer, 1990) and guinea-pig isolated jugular vein (Gupta, 1992). This suggests that the endothelial cells in some blood vessels may also possess a 5-HTI-like receptor with a pharmacological profile which is actually consistent with the vasoconstrictor subtype found on the vascular smooth muscle (for further discussion see Cambridge et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Studies in specific isolated blood vessels (Molderings et al, 1989;Schoeffter & Hoyer, 1990;Gupta, 1992) in vitro indicated that sumatriptan and 5-carboxamidotryptamine could elicit endothelial-dependent relaxation through the relese of nitric oxide (NO), the endothelial-derived vasodilator formerly known as EDRF (Khan & Furchgott, 1987;Ignarro et al, 1987;Palmer et al, 1987 (Whiting & Cambridge, 1991) (Green, 1979). …”

Section: Introductionmentioning

confidence: 99%

Canine renovascular responses to sumatriptan and 5‐carboxamidotryptamine: modulation through endothelial 5‐HT₁‐like receptors by endogenous nitric oxide

Whiting

Cambridge

1995

1 In anaesthetized dogs, intra-left atrial (i.l.a.) administration of the 5-HTI-like receptor agonists, sumatriptan (1-10 gkg-') and 5-carboxamidotryptamine (0.03-0.3plgkg-') produced dose-related reductions in renal blood flow and vascular conductance, which were characterized by their rapid onset and recovery. 2 In these animals, i.v. administration of the inhibitor of nitric oxide (NO) synthase, N0-nitro-Larginine methyl ester (L-NAME; 10 mg kg-') significantly augmented the renal vasoconstrictor responses to i.l.a. sumatriptan and 5-carboxamidotryptamine. 3 The effects of L-NAME upon these responses to sumatriptan and 5-carboxamidotryptamine were significantly reversed by subsequent i.v. administration of L-arginine (1000mgkg-'). 4 L-NAME-significantly attenuated the systemic hypotensive responses to i.v. acetylcholine (0.3-3 ,tg kg-') and this effect was also reversed by L-arginine. 5 L-NAME had no effect upon the renal vasoconstrictor response to i.l.a. administration of angiotensin II, nor did it affect the renal vascular conductance recovery response to brief mechanical occlusion of the renal artery. 6 These data suggest that sumatriptan and 5-carboxamidotryptamine stimulate the release of NO through the activation of a 5-HTI-like receptor located on the endothelial cells.7 It is concluded that in canine renal vasculature, 5-HT,-like agonists (and presumably endogenous 5-hydroxytryptamine) can cause simultaneous activation of a 5-HT,-like receptor on both vascular smooth muscle and endothelial cells. The net renal vascular response to these agonists is therefore a function of both the vascular smooth muscle vasoconstriction and the concurrent vasodilator influence of NO released from the endothelium.