5-HT1-Receptor-mediated Vasoconstriction in Bovine Isolated Pulmonary Arteries: Influences of Vascular Endothelium and Tone

MacLean, Margaret R.; Clayton, R.A.E.; Hillis, S; McIntyre, P.D.; Peacock, Andrew; Templeton, A.G.B.

doi:10.1006/pulp.1994.1007

Cited by 43 publications

(48 citation statements)

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“…Using 5-CT, we established that there is 5-HT-receptor-induced vasodilation present in the vessels from the 4-and 7-day-old rabbits. We have previously shown that pre-constriction of bovine pulmonary arteries can`uncover' 5-HT 1 -receptor-mediated vasoconstriction (MacLean et al, 1994;Sweeney et al, 1995). It is of interest, therefore, that no contractile responses to 5-CT were observed in the present study, indicating that under the conditions used, there was no uncovering of 5-HT 1 -receptor-mediated vasoconstriction these rabbit pre-constricted vessels.…”

Section: -Ht Receptor-induced Vasodilationmentioning

confidence: 48%

“…5-HT causes vasoconstriction in isolated bovine intrapulmonary arteries via a 5-HT 1D/1B receptor (MacLean et al, 1994) but induces endothelium-dependent relaxation in isolated porcine pulmonary arteries via the`5-HT 1C ' receptor (Glusa & Richter, 1993). The 5-HT 1C receptor has subsequently been renamed the 5-HT 2C receptor (Hoyer et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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

Morecroft

MacLean

1998

British J Pharmacology

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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.

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Section: -Ht Receptor-induced Vasodilationmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

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

Morecroft

MacLean

1998

British J Pharmacology

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“…However, recent studies have unveiled the participation of 5-HT 1B/1D receptors. Thus, in bovine isolated pulmonary arteries under conditions of basal tone, responses to 5-HT are exclusively mediated by activation of 5-HT 2A receptors while when tone was pharmacologically increased, a 5-HT 1B/1D response emerged to both 5-HT and sumatriptan (MacLean et al, 1994). The human isolated pulmonary artery is known to have very little or no spontaneous tone (Boe, 1982;Greenberg et al, 1987) although it responded with a strong contraction to 5-HT 1B/1D agonists like sumatriptan (MacLean et al, 1996).…”

Section: Contraction Of Human Pulmonary Vascular Preparations In Respmentioning

confidence: 93%

“…The vasoconstrictor eect of 5-HT in pulmonary vascular preparations isolated from dierent animal species including human has been ascribed to activation of 5-HT 2A receptors (Frenken & Kaumann, 1984;Raestin et al, 1985;Selig et al, 1988;MacLean et al, 1994). This assumption was mainly based in experiments where ketanserin or other 5-HT 2A receptor antagonists were used.…”

Section: Contraction Of Human Pulmonary Vascular Preparations In Respmentioning

confidence: 99%

“…Initially, results from animal and human studies indicate that the vasoconstrictor eect of 5-HT in pulmonary vascular preparations was mediated through 5-HT 2 receptors (Frenken & Kaumann, 1984;Raestin et al, 1985;Selig et al, 1988), more recently classi®ed as 5-HT 2A . However, recent studies revealed the involvement of 5-HT 1B/1D receptors in vasoconstrictor responses to 5-HT in bovine and human isolated pulmonary arteries (Maclean et al, 1994(Maclean et al, , 1996.…”

mentioning

confidence: 99%

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Characterization of 5‐HT receptors on human pulmonary artery and vein: functional and binding studies

Cortijo

Martı́-Cabrera

Bernabeu

et al. 1997

British J Pharmacology

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1 This study aimed to investigate the 5-hydroxytryptamine (5-HT) receptors mediating contraction of ring preparations isolated from human pulmonary arteries and veins. In functional studies, the responses to 5-HT, sumatriptan, ergotamine, serotonin-O-carboxymethyl-glycyl-tyrosinamide (SCMGT), a-methyl 5-HT (a-Me) and 2-methyl 5-HT (2-Me) were studied with WAY100635, GR127935, ritanserin, zacopride and SB204070 as antagonists. 2 All agonists produced concentration-dependent contractions of human pulmonary artery and vein preparations. The order of potency (7log EC 50 values) was ergotamine (6.88)45-HT (6.41)5SCMGT (6.20)=sumatriptan (6.19) 5a-Me (6.04) in the artery, and ergotamine (7.84)45-HT (6.96)4suma-triptan (6.60)=a-Me (6.56)4SCMGT (6.09) in the vein. The potency of each agonist, except for SCMGT, was greater in vein than in artery preparations. Contractile responses to 5-HT were similar in intact and endothelium-denuded preparations but responses to sumatriptan were enhanced in artery rings without endothelium. 3 GR127935 (1 nM to 0.5 mM) produced an unsurmountable antagonism of the response to 5-HT, sumatriptan, ergotamine and SCMGT. Ritanserin (1 nM to 1 mM) also reduced the maximum contractile responses to 5-HT, ergotamine and a-Me in artery and vein preparations without aecting those to sumatriptan and SCMGT. In endothelium-denuded preparations, surmountable antagonism of sumatriptan by GR127935 (in the presence of ritanserin) and of a-Me by ritanserin (in the presence of GR127935) allowed for the calculation of the apparent pK B values of GR127935 (9.17+0.11 in artery and 9.11+0.05 in vein) and ritanserin (8.82+0.09 in artery and 8.98+0.12 in vein). 4 WAY100635 (1 nM to 1 mM), zacopride (1 nM to 1 mM), or SB204070 (1 nM) did not signi®cantly alter the concentration-response curves for 5-HT, sumatriptan, ergotamine, SCMGT or 2-Me in human pulmonary artery or vein thus indicating that 5-HT 1A , 5-HT 3 and 5-HT 4 receptors are presumably not involved in the contractile response to these agonists. 5 Binding studies using selective radioligands for dierent 5-HT receptors could not detect the presence of 5-HT 1A receptor binding in human pulmonary blood vessels whereas the 5-HT 1B/1D radioligand [ 3 H]-5-CT signi®cantly labelled a population of speci®c binding sites in both vessel types. The presence of 5-HT 2A receptors could also be inferred from the level of binding of [ 3 H]-ketanserin to membranes obtained from human pulmonary vessels, although signi®cance could not be reached for arteries. 5-HT 4 speci®c receptor binding was scarce in veins and absent in the case of arteries. 6 These ®ndings indicate that the human pulmonary artery and vein have a mixed functional population of 5-HT 1B/1D and 5-HT 2A receptors mediating the contractile response to 5-HT which is consistent with results of the binding studies.

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Lung Circulation

Suresh

Shimoda

2016

Comprehensive Physiology

111

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The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed.

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5-HT1-Receptor-mediated Vasoconstriction in Bovine Isolated Pulmonary Arteries: Influences of Vascular Endothelium and Tone

Cited by 43 publications

References 0 publications

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

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

Characterization of 5‐HT receptors on human pulmonary artery and vein: functional and binding studies

Lung Circulation

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