Science China Life Sciences

, Volume 57, Issue 7, pp 681–689

Enhanced vasoconstriction to α1 adrenoceptor autoantibody in spontaneously hypertensive rats

Open AccessResearch Paper

DOI: 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−1−10 μmol L−1) were greater in SHR than in WKY rats. Endothelial denudation or L-NAME (a non-selective NOS inhibitor) (100 μmol L−1) increased α1-AA- or phenylephrine-induced vasoconstrictions both in SHR and WKY. However, selective iNOS inhibitor 1400W (10 μmol L−1) 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.

Keywords

autoimmunityadrenergic receptorblood vesselendotheliumprotein nitrationhypertension
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© The Author(s) 2014

Authors and Affiliations

  1. 1.Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medical Sciences Peking Union Medical CollegeBeijingChina
  2. 2.Key Laboratory of Medical Electrophysiology of Ministry of EducationLuzhou Medical CollegeLuzhouChina
  3. 3.The High School Affiliated to Renmin University of ChinaBeijingChina
  4. 4.Department of Pathophysiology, School of Basic Medical SciencesCapital Medical University, the Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of EducationBeijingChina