6533b7defe1ef96bd1275c4b

RESEARCH PRODUCT

Pathological role of a constitutively active population of α1D -adrenoceptors in arteries of spontaneously hypertensive rats

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The role of a constitutively active population of α1D-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. 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 α1D-adrenoceptors only in some vessels of SHR. The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of α1D-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR. In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed. The increase in the functional role of α1D-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 α1D-adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. British Journal of Pharmacology (2002) 135, 206–216; doi:10.1038/sj.bjp.0704447