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组成型活性α(1D)-肾上腺素能受体在自发性高血压大鼠动脉中的病理作用。

Pathological role of a constitutively active population of alpha(1D)-adrenoceptors in arteries of spontaneously hypertensive rats.

作者信息

Gisbert Regina, Ziani Khalid, Miquel Raquel, Noguera M Antonia, Ivorra M Dolores, Anselmi Elsa, D'Ocon Pilar

机构信息

Departamento de Farmacología, Facultad de Farmacia, Universitat de València, Spain.

出版信息

Br J Pharmacol. 2002 Jan;135(1):206-16. doi: 10.1038/sj.bjp.0704447.

Abstract
  1. The role of a constitutively active population of alpha(1D)-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg(-1) per day orally) in order to prevent the hypertensive state. 2. In adult SHR, a significant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the first and second branches of the small mesenteric arteries with respect to WKY rats. This difference was not observed in iliac and tail arteries, which suggests an increased functional role of alpha(1D)-adrenoceptors only in some vessels of SHR. 3. The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of alpha(1D)-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR. 4. In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed. 5. The increase in the functional role of alpha(1D)-adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active alpha(1D)-adrenoceptors. This change was not observed in prehypertensive or captopril treated animals.
摘要
  1. 分析了组成型活性α(1D)-肾上腺素能受体在自发性高血压大鼠(SHR)和对照组(WKY)动脉中的作用,这些大鼠分为三组:年轻的高血压前期、成年高血压以及成年动物长期用卡托普利(每天口服50 mg kg(-1))治疗以预防高血压状态。2. 在成年SHR中,与WKY大鼠相比,在主动脉、肠系膜动脉以及小肠系膜动脉的第一和第二分支中观察到BMY 7378效力显著增加(哌唑嗪效力未增加)。在髂动脉和尾动脉中未观察到这种差异,这表明α(1D)-肾上腺素能受体仅在SHR的某些血管中功能作用增强。3. 在无激动剂时观察到的静息张力增加(IRT),可被BMY 7378抑制,代表组成型活性α(1D)-肾上腺素能受体群体,在成年SHR的主动脉和肠系膜动脉中也显著更大。4. 在年轻和用卡托普利治疗的成年动物中,在BMY 7378效力或IRT方面未观察到品系间差异。5. 卡托普利治疗可预防高血压中观察到的α(1D)-肾上腺素能受体功能作用增加及其组成型活性。这种变化的病理后果是在去除肾上腺素能刺激后基础张力恢复速率较慢,在显示组成型活性α(1D)-肾上腺素能受体功能增加的高血压动物的血管中观察到这种情况。在高血压前期或用卡托普利治疗的动物中未观察到这种变化。

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