TY - JOUR
T1 - Pressor response induced by central angiotensin II is mediated by activation of Rho/Rho-kinase pathway via AT1 receptors
AU - Sagara, Yoji
AU - Hirooka, Yoshitaka
AU - Nozoe, Masatsugu
AU - Ito, Koji
AU - Kimura, Yoshikuni
AU - Sunagawa, Kenji
PY - 2007/2
Y1 - 2007/2
N2 - OBJECTIVES: The brain renin-angiotensin system plays an important role in cardiovascular regulation and the pathogenesis of hypertension. Angiotensin II activates the Rho/Rho-kinase pathway in vascular smooth muscle cells and cardiomyocytes in vitro. The aim of the present study was to determine whether angiotensin II in the brainstem activates the Rho/Rho-kinase pathway, and, if so, whether this mechanism is involved in the central pressor action of angiotensin II. METHODS AND RESULTS: Angiotensin II infused intracisternally for 7 days in Wistar-Kyoto rats (WKY) increased systolic blood pressure (SBP) and urinary norepinephrine excretion. These responses were abolished by the co-infusion of Y-27632, a specific Rho-kinase inhibitor, or valsartan. The intracisternal infusion of Y-27632 or valsartan also reduced SBP and norepinephrine excretion in spontaneously hypertensive rats (SHR). Western blot analysis was performed to examine the expression levels of membranous RhoA and phosphorylated ezrin, radixin, and moesin (p-ERM), which reflects Rho/Rho-kinase activity. The expression levels of membranous RhoA and p-ERM in the brainstem were significantly greater in both angiotensin II-treated WKY and SHR than in vehicle-treated WKY. Valsartan reduced the expression levels of membranous RhoA and p-ERM in angiotensin II-treated WKY and SHR. Y-27632 reduced the expression levels of p-ERM in angiotensin II-treated WKY and SHR. CONCLUSIONS: These results suggest that the pressor response induced by intracisternally infused angiotensin II is substantially mediated by the activation of the Rho/Rho-kinase pathway via AT1 receptors of the brainstem in WKY, and that this pathway might be involved in the hypertensive mechanisms of SHR.
AB - OBJECTIVES: The brain renin-angiotensin system plays an important role in cardiovascular regulation and the pathogenesis of hypertension. Angiotensin II activates the Rho/Rho-kinase pathway in vascular smooth muscle cells and cardiomyocytes in vitro. The aim of the present study was to determine whether angiotensin II in the brainstem activates the Rho/Rho-kinase pathway, and, if so, whether this mechanism is involved in the central pressor action of angiotensin II. METHODS AND RESULTS: Angiotensin II infused intracisternally for 7 days in Wistar-Kyoto rats (WKY) increased systolic blood pressure (SBP) and urinary norepinephrine excretion. These responses were abolished by the co-infusion of Y-27632, a specific Rho-kinase inhibitor, or valsartan. The intracisternal infusion of Y-27632 or valsartan also reduced SBP and norepinephrine excretion in spontaneously hypertensive rats (SHR). Western blot analysis was performed to examine the expression levels of membranous RhoA and phosphorylated ezrin, radixin, and moesin (p-ERM), which reflects Rho/Rho-kinase activity. The expression levels of membranous RhoA and p-ERM in the brainstem were significantly greater in both angiotensin II-treated WKY and SHR than in vehicle-treated WKY. Valsartan reduced the expression levels of membranous RhoA and p-ERM in angiotensin II-treated WKY and SHR. Y-27632 reduced the expression levels of p-ERM in angiotensin II-treated WKY and SHR. CONCLUSIONS: These results suggest that the pressor response induced by intracisternally infused angiotensin II is substantially mediated by the activation of the Rho/Rho-kinase pathway via AT1 receptors of the brainstem in WKY, and that this pathway might be involved in the hypertensive mechanisms of SHR.
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U2 - 10.1097/HJH.0b013e328010b87f
DO - 10.1097/HJH.0b013e328010b87f
M3 - Article
C2 - 17211247
AN - SCOPUS:33846037819
VL - 25
SP - 399
EP - 406
JO - Journal of Hypertension
JF - Journal of Hypertension
SN - 0263-6352
IS - 2
ER -