Effect of cooling on vascular smooth muscle response to endothelin-1 in human and rat veins

BACKGROUND: The plasma level of endothelin-1 is locally increased during cooling but the net vasoconstrictor effect will be dependent on temperature effects on the vascular smooth muscle reactivity in response to the polypeptide. The aim of this study was to investigate the effect of cooling on the vascular smooth muscle response to endothelin-1 in human and rat veins. METHODS: Registration of vascular smooth muscle activity in vitro in vessel preparations from normal subjects. SETTING: Laboratory. PATIENTS AND ANIMALS: Superficial hand veins from 14 patients undergoing hand surgery and external jugular veins from 14 rats. INTERVENTIONS: Effects of endothelin-1, after denudation of the endothelium and during cooling, were compared with controls without these interventions. RESULTS: At 37 degrees C, endothelin-1 induced a concentration-dependent contraction in the human hand and rat jugular veins. The sensitivity to endothelin-1 was enhanced in segments without endothelium. At 37 degrees C, no relaxation in response to endothelin-1 was observed. Cooling to 10 degrees C did not alter precontraction achieved by endothelin-1 at 37 degrees C in the human hand veins, while it depressed the precontraction in the rat jugular vein. The effect of cold was reversible. Removal of the endothelium did not alter the response to cooling. CONCLUSIONS: The maintained reactivity in response to endothelin-1 during cooling of the human vessels suggests that the reported increase in endothelin-1 levels due to local cooling could contribute in the pathophysiology of peripheral vasospasm in humans

The objective diagnosis of vibration-induced vascular injury

For 44 patients with vibration-induced white finger and a reference group of 25 healthy men, finger systolic blood pressure (FSBP) before and after local cooling, skin temperature, and rewarming rates were determined before and after vasodilation (body warming and alcohol). An estimation of the proportions of vasopasm and organic changes was possible, and cutaneous changes could be separated from changes in the main digital vessels. The arm blood pressure was higher for the patients and the fingertip temperatures were lower, but both normalized after vasodilation. The FSBP values were equal in the two groups before local cooling. Afterward the patients had lower FSBP values which remained unchanged after the postvasodilatation cooling. Ten patients, all smokers, reacted with complete arterial closure after local cooling. When this group was separated from the other smoking patients, there was no significant difference between the smoking and nonsmoking patients, and the FSBP differences between the patients and referents was almost eliminated. It was concluded that, in vibration-exposed patients, injuries to skin circulation seem to be more frequent than injuries to the main digital vessels, except for some smokers, who have severe vasopasm combined with organic changes

Cooling augments contractile response to 5-hydroxytryptamine via an endothelium-dependent mechanism

The interaction between cooling and vasoactive substances, e.g. 5-hydroxytryptamine (5-HT), plays an important role in the pathophysiology of cold-induced vasospasm. Our objective was to study the effect of cooling on the 5-HT vascular response, classify the involved 5-HT receptors, and to analyze the role of the endothelium. Ring segments from the rat jugular vein, a preparation without alpha-adrenergic receptors, were suspended in organ baths to record the circular motor activity. The temperature was initially 37 degrees C and was thereafter either continuously lowered to 10 degrees C or kept constant at different temperatures within this range. 5-HT at low concentrations (10(-11) to 3 x 10(-8) M) induced relaxation at 37 degrees C in segments precontracted by prostaglandin F2 alpha. The relaxation was recognized to be mediated via an endothelium-dependent 5-HT1-like receptor mechanism presumably involving the release of endothelium-derived relaxing factor (EDRF). Cooling to 29 and 20 degrees C diminished the relaxation, probably due to an attenuated release of EDRF. 5-HT at concentrations of more than 10(-8) M induced a contraction in all vessels at 37 degrees C mediated via a 5-HT2 receptor. An increased 5-HT-induced contraction was seen at temperatures below 37 degrees C in vessels with an intact endothelium. Endothelial denudation diminished the cold-induced enhancement of the contraction to 5-HT. These studies suggest that endothelial mechanisms contribute to a cold-induced augmented response to 5-HT

Effect of cooling on smooth muscle response to 5-hydroxytryptamine in human hand veins

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

Cooling enhances alpha 2-adrenoceptor-mediated vasoconstriction in human hand veins

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

Differential effect of hypothermia on the vascular tone and reactivity of the human coronary artery and graft vessels

Hypothermia may contribute to vascular spasm during bypass surgery. The effect of cooling on the reactivity of the human coronary artery (CA), saphenous vein (SV) and internal mammary artery (IMA) was studied in vitro. In CA and IMA cooling diminished the resting tension and the contraction to potassium, noradrenaline and 5-hydroxytryptamine. In contrast, in SV the contraction to noradrenaline and 5-hydroxytryptamine was augmented by cooling. The effect of cold was reversible. These results demonstrate different effects of hypothermia in CA and the graft vessels. Thus, hypothermia augments the receptor-mediated contraction in SV but depresses it in IMA which thereby resembles CA. The difference is most marked in the contractile response to 5-hydroxytryptamine, which may accumulate during surgery. This may contribute to spasm in the saphenous vein grafts and may be involved in the mechanisms responsible for the inferior patency of SV compared to IMA as a graft vessel