Pyk2 mediates increased adrenergic contractile responses in arteries from DOCA-salt mice - VASOACTIVE PEPTIDE SYMPOSIUM

Fernanda R C Giachini; Fernando S Carneiro; Victor V Lima; Zidonia N Carneiro; Maria Helena C Carvalho; Zuleica B Fortes; R Clinton Webb; Rita C Tostes

doi:10.1016/j.jash.2008.05.001

Pyk2 mediates increased adrenergic contractile responses in arteries from DOCA-salt mice - VASOACTIVE PEPTIDE SYMPOSIUM

J Am Soc Hypertens. 2008 Nov-Dec;2(6):431-8. doi: 10.1016/j.jash.2008.05.001.

Authors

Fernanda R C Giachini¹, Fernando S Carneiro, Victor V Lima, Zidonia N Carneiro, Maria Helena C Carvalho, Zuleica B Fortes, R Clinton Webb, Rita C Tostes

Affiliation

¹ Medical College of Georgia, Department of Physiology, Augusta, GA, USA, 30904.

Abstract

Background: The calcium-dependent proline-rich tyrosine kinase (Pyk2), a nonreceptor protein activated by tyrosine phosphorylation, links G protein-coupled receptors to vascular responses. We tested the hypothesis that enhanced vascular reactivity in DOCA-salt hypertensive mice are due to increased activation of Pyk2.

Methods and results: Aorta and small mesenteric arteries from DOCA-salt and uninephrectomized (UNI) male C57Bl/6 mice were used. Systolic blood pressure (mmHg) was higher in DOCA (126+/-3) vs. UNI (100+/-4) mice. Vascular responses to phenylephrine (1nM to 100muM) were greater both in aorta and small mesenteric arteries from DOCA-salt than UNI, but treatment with Tyrphostin A-9 (0.1muM, Pyk2 inhibitor) abolished the difference among the groups. Pyk2 levels, as well as phospho-Pyk2(Tyr402), paxillin and phospho-paxillin(Tyr118) were increased in DOCA-salt aorta. Incubation of vessels with Tyrphostin A-9 restored phosphorylation of Pyk2 and paxillin.

Conclusion: Increased activation of Pyk2 contributes to increased vascular contractile-responses in DOCA-salt mice.

Keywords: Hypertension; Pyk2 and DOCA-salt; paxillin.

Abstract

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