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四氧嘧啶诱导的糖尿病大鼠脑血管中增强的肾上腺素能反应。

Enhanced adrenergic response of the cerebral vasculature in alloxan-induced diabetic rats.

作者信息

Kurihara J, Hosono M, Kato H

机构信息

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.

出版信息

J Pharmacobiodyn. 1989 Nov;12(11):700-7. doi: 10.1248/bpb1978.12.700.

Abstract

The influence of alloxan-induced diabetes on the adrenergic constriction of the rat cerebral vasculature was investigated in the in situ perfused brain preparation. The preparation was perfused with an artificial medium at a constant flow rate and the change in perfusion pressure was measured. Norepinephrine (NE) and serotonin produced a dose-dependent increase in the perfusion pressure, but only the effect of NE was significantly enhanced in the diabetic rats. Such an enhancement of NE-induced vasoconstriction was not observed in the perfused hindquarter preparations from the diabetic rats. Propranolol (1 microM) potentiated the cerebrovascular constriction by NE and abolished the difference between diabetic and control rats at low doses of NE. However, vasoconstriction by the higher doses of NE in the diabetic rats was still enhanced even in the presence of propranolol. The cerebrovascular constriction by phenylephrine was also enhanced in the diabetic rats, while the vasoconstricting effects of clonidine, xylazine and oxymetazoline were not affected by diabetes. These results suggest that the enhanced cerebrovascular constriction by NE may be due to either the reduced response through beta-adrenoceptors or the enhanced response through alpha 1-adrenoceptors. The enhanced adrenergic constriction of the cerebral vasculature might be concerned with the high incidence of neurological deficit in stroke patients with diabetes.

摘要

在原位灌流脑标本中研究了四氧嘧啶诱导的糖尿病对大鼠脑血管肾上腺素能收缩的影响。以恒定流速用人工介质灌流该标本,并测量灌注压力的变化。去甲肾上腺素(NE)和5-羟色胺使灌注压力呈剂量依赖性增加,但仅NE的作用在糖尿病大鼠中显著增强。在糖尿病大鼠的灌流后肢标本中未观察到NE诱导的血管收缩增强。普萘洛尔(1 microM)增强了NE引起的脑血管收缩,并消除了低剂量NE时糖尿病大鼠和对照大鼠之间的差异。然而,即使存在普萘洛尔,糖尿病大鼠中高剂量NE引起的血管收缩仍增强。苯肾上腺素引起的脑血管收缩在糖尿病大鼠中也增强,而可乐定、赛拉嗪和羟甲唑啉的血管收缩作用不受糖尿病影响。这些结果表明,NE引起的脑血管收缩增强可能是由于β-肾上腺素能受体反应降低或α1-肾上腺素能受体反应增强。脑血管肾上腺素能收缩增强可能与糖尿病中风患者神经功能缺损的高发生率有关。

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