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Science China Life Sciences

, Volume 57, Issue 7, pp 681–689

First Online: 20 June 2014Received: 01 November 2013Accepted: 02 December 2013DOI: 10.1007-s11427-014-4672-8

Cite this article as: Yan, L., Tan, X., Chen, W.
et al.
Sci.
China Life Sci.
2014 57: 681.
doi:10.1007-s11427-014-4672-8

Abstract

Autoimmune activities have been implicated in the pathogenesis of hypertension.
High levels of autoantibodies against the second extracellular loop of α1-adrenoceptor α1-AR autoantibody, α1-AA are found in patients with hypertension, and α1-AA could exert a α1-AR agonist-like vasoconstrictive effect.
However, whether the vasoconstrictive effect of α1-AA is enhanced in hypertension is unknown.
Using aortic rings of spontaneously hypertensive rats SHR and normotensive Wistar-Kyoto WKY rats, we observed the vasoconstrictive responses to α1-AA with phenylephrine α1-AR agonist as a positive control drug.
Aortic nitrotyrosine levels were also measured by ELISA and immunohistochemistry.
The results showed that the aortic constrictive responses to α1-AA and phenylephrine both 1 nmol L−10 μmol L were greater in SHR than in WKY rats.
Endothelial denudation or L-NAME a non-selective NOS inhibitor 100 μmol L increased α1-AA- or phenylephrine-induced vasoconstrictions both in SHR and WKY.
However, selective iNOS inhibitor 1400W 10 μmol L enhanced the α1-AA-induced aortic constriction in WKY, but not in SHR.
The aortic nitrotyrosine level was significantly higher in SHR than WKY, as shown by both ELISA and immunohistochemistry.
These results indicate that the vasoconstrictive response to α1-AA is enhanced in SHR, and this altered responsiveness is due to endothelial dysfunction and decreased NO bioavailability.
The study suggests an important role of α1-AR autoimmunity in the pathogenesis and management of hypertension especially in those harboring high α1-AA levels.

Keywordsautoimmunity adrenergic receptor blood vessel endothelium protein nitration hypertension Contributed equally to this work

This article is published with open access at link.springer.com

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Autor: Li Yan - XiaoQiu Tan - WenXuan Chen - Hong Zhu - JiMin Cao - HuiRong Liu

Fuente: https://link.springer.com/



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