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Adventitia removal does not modify the α1D-adrenoceptors response in aorta during hypertension and ageing

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Abstract:

Summary

1 The aim of the current study was to characterize the α1-adrenergic receptors (α1-ARs) present in the isolated tunica media of aorta, in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats during the course of ageing and hypertension (rats of 1, 3, 6 and 12 months of age). In all vessels, endothelium was removed.

2 In isolated aortic rings, phenylephrine increased contraction in a concentration- and age-dependent manner and was impaired in old SHR compared with WKY rats.

3 The α1-AR selective antagonist prazosin showed high affinity (pA2) in vessels from both rat strains.

4 The potency of the α1A-AR selective antagonists, RS 100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl] propyl]-2,4-(1H)-pyrimidinedione) and 5-methylurapidil in antagonizing aortic phenylephrine-responses was low.

5 The α1D-AR selective antagonist, BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1 piperazynil] ethyl]-8-azaspiro [4.5] decane-7,9-dione) potently blocked phenylephrine-induced responses in aorta from both strains and at all ages.

6 Adventitia removal decreased Emax in older rats and modified the relative affinity (pD2), but did not affect the affinity of the selective antagonists.

7 The results suggest that aorta tunica α1D-AR is the main subtype involved in phenylephrine-induced contraction of rat aorta, while α1A-AR plays only a minor role.

8 Ageing and hypertension did not modify α1-ARs in the blood vessel and the tunica adventitia does not seem to participate in contraction, even though α1-ARs are expressed.

Keywords: SHR; ageing; hypertension; α1-adrenoceptors; α1D-adrenoceptors aortic media layer

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1474-8673.2009.00432.x

Publication date: July 1, 2009

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