TY - JOUR
T1 - Pyk2 mediates increased adrenergic contractile responses in arteries from DOCA-salt mice - Vasoactive Peptide Symposium
AU - Giachini, Fernanda R.C.
AU - Carneiro, Fernando S.
AU - Lima, Victor V.
AU - Carneiro, Zidonia N.
AU - Carvalho, Maria Helena C.
AU - Fortes, Zuleica B.
AU - Webb, R. Clinton
AU - Tostes, Rita C.
N1 - Funding Information:
This study was supported by Grants from the National Institutes of Health (NIH HL71138 and HL74167) and Fundacao de Amparo a Pesquisa do Estado de São Paulo — FAPESP, Brazil.
PY - 2008/11
Y1 - 2008/11
N2 - 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 deoxycorticosterone acetate (DOCA)-salt hypertensive mice is due to increased activation of Pyk2. Aorta and small mesenteric arteries from DOCA-salt and uninephrectomized (UNI) male C57Bl/6 mice were used. Systolic blood pressure (mm Hg) was higher in DOCA (126 ± 3) vs. UNI (100 ± 4) mice. Vascular responses to phenylephrine (1 nM to 100 μM) were greater both in aorta and small mesenteric arteries from DOCA-salt than UNI, but treatment with Tyrphostin A-9 (0.1 μM, Pyk2 inhibitor) abolished the difference among the groups. Pyk2 levels, as well as phospho-Pyk2Tyr402, paxillin, and phospho-paxillinTyr118 were increased in DOCA-salt aorta. Incubation of vessels with Tyrphostin A-9 restored phosphorylation of Pyk2 and paxillin. Increased activation of Pyk2 contributes to increased vascular contractile responses in DOCA-salt mice.
AB - 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 deoxycorticosterone acetate (DOCA)-salt hypertensive mice is due to increased activation of Pyk2. Aorta and small mesenteric arteries from DOCA-salt and uninephrectomized (UNI) male C57Bl/6 mice were used. Systolic blood pressure (mm Hg) was higher in DOCA (126 ± 3) vs. UNI (100 ± 4) mice. Vascular responses to phenylephrine (1 nM to 100 μM) were greater both in aorta and small mesenteric arteries from DOCA-salt than UNI, but treatment with Tyrphostin A-9 (0.1 μM, Pyk2 inhibitor) abolished the difference among the groups. Pyk2 levels, as well as phospho-Pyk2Tyr402, paxillin, and phospho-paxillinTyr118 were increased in DOCA-salt aorta. Incubation of vessels with Tyrphostin A-9 restored phosphorylation of Pyk2 and paxillin. Increased activation of Pyk2 contributes to increased vascular contractile responses in DOCA-salt mice.
KW - Hypertension
KW - noradrenaline
KW - paxillin
KW - vascular smooth muscle cell
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U2 - 10.1016/j.jash.2008.05.001
DO - 10.1016/j.jash.2008.05.001
M3 - Article
C2 - 19884968
AN - SCOPUS:57149086456
SN - 1933-1711
VL - 2
SP - 431
EP - 438
JO - Journal of the American Society of Hypertension
JF - Journal of the American Society of Hypertension
IS - 6
ER -