title: Pressor response induced by central angiotensin II is mediated by activation of Rho/Rho-kinase pathway via AT1 receptors.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sagara
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Nozoe
authors.forename: Koji
authors.initials: K
authors.lastname: Ito
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D001933:Brain Stem / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D009638:Norepinephrine / Q000652:urine; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000032:analysis / Q000378:metabolism
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D009638:Norepinephrine