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.
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-salthypertensivemice 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-saltmice.
Entities:
Keywords:
Hypertension; Pyk2 and DOCA-salt; paxillin
Authors: Victor V Lima; Fernanda R Giachini; Fernando S Carneiro; Zidonia N Carneiro; Mohamed A Saleh; David M Pollock; Zuleica B Fortes; Maria Helena C Carvalho; Adviye Ergul; R Clinton Webb; Rita C Tostes Journal: Hypertension Date: 2009-11-30 Impact factor: 10.190
Authors: Victor V Lima; Fernanda R C Giachini; Hyehun Choi; Fernando S Carneiro; Zidonia N Carneiro; Zuleica B Fortes; Maria Helena C Carvalho; R Clinton Webb; Rita C Tostes Journal: Hypertension Date: 2009-01-12 Impact factor: 10.190
Authors: Sunila Mahavadi; Ancy D Nalli; Hongxia Wang; Derek M Kendig; Molly S Crowe; Vijay Lyall; John R Grider; Karnam S Murthy Journal: PLoS One Date: 2018-12-20 Impact factor: 3.240