Salicylates dilate blood vessels through inhibiting PYK2-mediated RhoA/Rho-kinase activation

Zhekang Ying, Fernanda R.C. Giachini, Rita C. Tostes, Robert Clinton Webb

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Aims: Compared with other non-steroid anti-inflammatory drugs (NSAIDs), aspirin is not correlated to hypertension. It has been shown that aspirin has unique vasodilator action in vivo, offering an explanation for the unique blood pressure effect of aspirin. In the present study, we investigate the mechanism whereby salicylates (aspirin and sodium salicylate) dilate blood vessels. Methods and results: Rat aortic or mesenteric arterial rings were used to test the vascular effect of salicylates and other NSAIDs. RhoA translocation and the phosphorylation of MYPT1, the regulatory subunit of myosin light chain phosphatase, were measured by western blot, as evidenced for RhoA/Rho-kinase activation. Salicylates, but not other NSAIDs, relaxed contraction induced by most tested constrictors except for calyculin A, indicating that RhoA/Rho-kinase-mediated calcium sensitization is involved. The involvement of RhoA/Rho kinase in vasodilation by salicylates was confirmed by measurements of RhoA translocation and MYPT1 phosphorylation. The calculated half maximal inhibitory concentration (IC50) of vasodilation was apparently higher than that of cyclooxygenase inhibition, but comparable to that of proline-rich tyrosine kinase 2 (PYK2) inhibition. Over-expression of PYK2 induced RhoA translocation and MYPT1 phosphorylation, and these effects were markedly inhibited by sodium salicylate treatment. Consistent with the ex vitro vascular effects, sodium salicylate acutely decreased blood pressure in spontaneous hypertensive rats but not in Wistar Kyoto rats. Conclusion: Salicylates dilate blood vessels through inhibiting PYK2-mediated RhoA/Rho-kinase activation and thus lower blood pressure.

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalCardiovascular Research
Volume83
Issue number1
DOIs
StatePublished - Jul 1 2009

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Keywords

  • Contractile function
  • G proteins
  • Hypertension
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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