| 1. |
- Bodelsson, Mikael, et al.
(författare)
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Cooling enhances alpha 2-adrenoceptor-mediated vasoconstriction in human hand veins
- 1990
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 138:3, s. 283-291
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of different receptor subtypes in the contractile response during cooling in human hand vessels is of considerable interest in the understanding of cold-induced peripheral vasospasm as it appears in Raynaud's phenomenon. Subcutaneous vein segments from 50 patients undergoing hand operations not related to vascular disorders were examined in vitro. The temperature in the organ bath was initially 37 degrees C and was either continuously lowered to 10 degrees C or kept constant at 37 degrees C, 29 degrees C or 20 degrees C. The characteristics of the alpha-adrenoceptor-mediated motor response were elucidated with the use of the alpha 1-antagonist, prazosin, and the alpha 2-antagonist, yohimbine. A great variability between individuals in the proportions of alpha 1- and alpha 2-adrenoceptors was found. In the majority of the vessels continuous cooling to 25 degrees C augmented a noradrenaline-induced contraction. This augmentation was unaltered in the presence of prazosin but abolished by yohimbine, suggesting that it was mediated via the alpha 2-adrenoceptor. In the remaining vessels with a predominating alpha 1-adrenoceptor-mediated response a cold-induced relaxation was registered. This could be the result of a reduced alpha 1-adrenoceptor-mediated contraction at this low temperature. These varying reactions to cooling were unaffected by the beta-antagonist, propranolol, and by endothelial denudation. The results obtained in corresponding experiments with the alpha 1-agonist methoxamine and alpha 2-agonist, oxymetazoline, were conflicting, probably due to the poor selectivity of these agonists in human tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 2. |
- Bodelsson, Mikael, et al.
(författare)
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Effect of cooling on smooth muscle response to 5-hydroxytryptamine in human hand veins
- 1990
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 140:3, s. 331-339
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Tidskriftsartikel (refereegranskat)abstract
- 5-Hydroxytryptamine has been suggested to be a mediator in peripheral cold-induced vasospasm. In order to investigate the contribution of different 5-hydroxytryptamine receptor subtypes in the contractile response during cooling, segments of subcutaneous hand veins obtained from 50 patients undergoing hand surgery were examined in vitro in organ baths. The temperature in the bath was initially 37 degrees C and was either continuously lowered to 10 degrees C or kept constant at 37 degrees C, 29 degrees C. Cooling to 25 degrees C augmented the contractile response to 5-hydroxytryptamine in intact as well as in endothelium-denuded segments. The 5-hydroxytryptamine2 receptor antagonist ketanserin antagonized the contractile response to 5-hydroxytryptamine at 37 degrees C, and in addition abolished the cold-induced enhancement of the response during cooling. This points to a major role of the 5-hydroxytryptamine2 receptor in the cold-induced augmentation of the response to 5-hydroxytryptamine, which was further supported by increased contractions to the 5-hydroxytryptamine2 receptor agonist alpha-methyl-5-hydroxytryptamine during cooling. Contractile responses were also obtained by the selective 5-hydroxytryptamine1-like receptor agonist GR43175 interpreted to indicate the presence of a smaller 5-hydroxytryptamine1-like receptor population. However, the response to GR43175 was unaffected by cooling. These results warrant further investigations of the role of 5-hydroxytryptamine in cold-induced peripheral vasospasm.
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| 3. |
- Chester, Adrian H, et al.
(författare)
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5-Hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries
- 1990
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 24:11, s. 932-937
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVE--The aim of the study was to investigate the receptor events that mediate the vascular effects of 5-hydroxytryptamine (5-HT) on human coronary arteries, since 5-HT has long been thought to play a role in coronary artery vasospasm. DESIGN--Recently available selective receptor agonists and antagonists were used to examine the 5-HT receptor subtypes present in human epicardial coronary arteries using in vitro organ baths. EXPERIMENTAL MATERIAL--138 segments of coronary arteries were obtained from 21 patients aged 2-66 years undergoing heart transplantation. MEASUREMENTS AND MAIN RESULTS--5-HT produced only concentration dependent contractions of coronary artery segments. No evidence was obtained for 5-HT receptors mediating either endothelium dependent or endothelium independent vasorelaxation. In tissue from patients without ischaemic heart disease, 5-HT effects were mimicked by (+/-)-alpha-methyl-5-HT (alpha-me-5-HT), a selective agonist at 5-HT2 receptors. In addition, the selective 5-HT1-like receptor agonist GR43175 produced contractions which achieved 30% of the maximum response to 5-HT. Responses to alpha-me-5-HT were surmountably antagonised by the non-selective antagonist methiothepin (0.1 mumol.litre-1) as well as the 5-HT2 receptor antagonist ketanserin (0.1 mumol.litre-1). In contrast GR43175 effects were resistant to blockade by ketanserin, but remained sensitive to methiothepin. Responses to the two agonists were not antagonised by the 5-HT3 receptor antagonist MDL72222 (1.0 mumol.litre-1). Vessel segments from ischaemic heart disease patients also contracted to alpha-me-5-HT and GR43175. Diseased arteries contracted with a decrease in the maximal response induced by both alpha-me-5-HT and by 90 mM K+ depolarisation compared to "normal" vessels, but the effect of GR43175 was preserved in the diseased arteries. Vascular rings adjacent to an atheromatous lesion were more reactive to GR43175 than serial segments taken distal to the lesion. CONCLUSIONS--These results show that both 5-HT1-like and 5-HT2 receptors mediate contraction of human epicardial coronary arteries and indicate that effects mediated by 5-HT1-like receptors but not 5-HT2 receptors are preserved in patients with ischaemic heart disease.
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