title: Evidence that estrogen suppresses rho-kinase function in the cerebral circulation in vivo.
abstract: OBJECTIVE
  Premenopausal women are less susceptible to cardiovascular diseases than men or postmenopausal women. Such disease states are often associated with increased vascular RhoA/Rho-kinase activity and decreased activity of nitric oxide (NO). This study tested whether female gender is associated with lower Rho-kinase activity or higher NO activity in cerebral arteries in vivo and whether estrogen contributes to any such gender differences.
  
  
  METHODS
  Changes in basilar artery diameter were measured with the use of a cranial window preparation in anesthetized Sprague-Dawley rats. Some female rats were ovariectomized (OVX) and treated subcutaneously daily for 14 days with vehicle (dimethyl sulfoxide) or 17beta-estradiol. Vascular expression of RhoA or Rho-kinase was assessed by Western blotting.
  
  
  RESULTS
  The Rho-kinase inhibitor Y-27632 was selectively approximately 3-fold more potent as a cerebral vasodilator in males versus females. Expression of total RhoA or Rho-kinase did not differ between males and females. In OVX rats, vasodilator responses to Y-27632 resembled responses in males. Treatment of OVX rats with 17beta-estradiol normalized the vasodilator effects of Y-27632 to be equivalent to responses in intact female controls. The NO synthase inhibitor N-nitro-l-arginine methyl ester caused approximately 50% greater constriction of the basilar artery in females versus males, but responses in OVX rats treated with either vehicle or 17beta-estradiol did not differ from those recorded in intact females.
  
  
  CONCLUSIONS
  These data indicate that vascular Rho-kinase function is suppressed in females because of the effects of estrogen, whereas the higher NO activity in females is estrogen independent.
authors.affiliation: Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Sophocles
authors.initials: S
authors.lastname: Chrissobolis
authors.forename: Klaudia
authors.initials: K
authors.lastname: Budzyn
authors.forename: Philip D
authors.initials: PD
authors.lastname: Marley
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010052:Ovariectomy; D010847:Picolines / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D011714:Pyrans / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000577:Amides; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D020030:Nitric Oxide Donors; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; D011725:Pyridines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C108830:Y 27632; D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; C061043:aprikalim; D004958:Estradiol; D009553:Nimodipine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester