title: Increased activity of calcium channels and Rho-associated kinase in the basilar artery during chronic hypertension in vivo.
abstract: OBJECTIVE
  Several factors mediating vascular responses appear to play an important role in the increased resistance of cerebral blood vessels during hypertension. The objective of this study was to elucidate the mechanisms by which hypertension increases the basal tone of the basilar artery in vivo.
  
  
  METHODS
  Using a cranial window, we examined effects of inhibitors of L-type voltage-dependent calcium channels (nicardipine) and Rho-associated kinase (Y-27632) on the baseline diameter of the basilar artery in spontaneously hypertensive rats (SHR) and compared to the responses in normotensive Wistar-Kyoto (WKY) rats.
  
  
  RESULTS
  Topical application of nicardipine (10(-8), 10(-7) and 10(-6) mol/l) produced dilatation of the basilar artery. Nicardipine-induced vasodilatation was enhanced in SHR compared to WKY rats. Nicardipine (10-6 mol/l) dilated the artery in WKY rats and SHR by 9 +/- 2 and 24 +/- 4%, respectively. Topical application of Y-27632 (10(-7), 10(-6) and 10(-5) mol/l) produced dilatation of the basilar artery in WKY rats in a concentration-related manner. The vasodilatation produced by Y-27632 was markedly enhanced in SHR compared to WKY rats. Y-27632 (10(-5) mol/l) dilated the artery in WKY rats and SHR by 14 +/- 2 and 45 +/- 6%, respectively. We also tested the effects of inhibitors of nitric oxide synthase (NG-nitro-l-arginine methyl ester, l-NAME), ATP-sensitive potassium channels (glibenclamide) and large-conductance calcium-activated potassium channels (tetraetyhlammonium, TEA). l-NAME and, to a lesser extent, glibenclamide produced similar constriction of the basilar artery in both strains. TEA did not affect the baseline diameter of the basilar artery in WKY rats and produced small but significant vasoconstriction in SHR.
  
  
  CONCLUSIONS
  These results suggest that the activity of L-type calcium channels and Rho-associated kinase is enhanced in the basilar artery during hypertensionin vivo. The enhanced contractility may contribute to the increased resistance of the basilar artery during chronic hypertension in vivo.
authors: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kitazono@intmed2.kyushu-u.ac.jp
authors: Takanari
authors: T
authors: Kitazono
authors: Tetsuro
authors: T
authors: Ago
authors: Masahiro
authors: M
authors: Kamouchi
authors: Naohiko
authors: N
authors: Santa
authors: Hiroaki
authors: H
authors: Ooboshi
authors: Masatoshi
authors: M
authors: Fujishima
authors: Setsuro
authors: S
authors: Ibayashi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D054460:rho-Associated Kinases
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D014662:Vasoconstrictor Agents; C108830:Y 27632; D012701:Serotonin; D009529:Nicardipine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester