title: Vessel- and vasoconstrictor-dependent role of rho/rho-kinase in renal microvascular tone.
abstract: We examined the role of Rho/Rho-kinase in renal afferent and efferent arteriolar tone induced by angiotensin (Ang) II, KCl and elevated renal arterial pressure (from 80 to 180 mm Hg), using isolated perfused rat hydronephrotic kidney. In the condition with no vasoconstrictor stimuli, Y-27632, a Rho-kinase inhibitor, dilated only afferent (from 11.6 +/- 0.4 to 14.1 +/- 0.5 microm) but not efferent arterioles (from 11.6 +/- 0.2 to 12.6 +/- 0.7 microm) at 10(-5) mol/l. During renal vasoconstriction by Ang II, Y-27632 restored the afferent arteriolar constriction (141 +/- 10% reversal at 10(-5) mol/l), whereas the ability of Y-27632 to inhibit the Ang II-induced efferent arteriolar constriction was diminished (73 +/- 7% reversal). A similar action was observed with fasudil, another Rho-kinase inhibitor. Furthermore, Y-27632 impaired myogenic afferent arteriolar constriction, with 117 +/- 17% inhibition at 10(-5) mol/l. The inhibition by Y-27632 of the myogenic vasoconstriction was almost the same as that of the Ang II-induced tone of this vessel type. However, Y-27632 had a modest effect on KCl-induced vasoconstriction of afferent arterioles. In conclusion, the present study demonstrates a predominant role of Rho/Rho-kinase in mediating the basal and Ang II-induced tone of afferent, but not efferent, arterioles. Furthermore, the role of Rho/Rho-kinase in afferent arteriolar constriction differs, with a substantial contribution to Ang II-induced and myogenic constriction but a minimal role in depolarization-induced constriction. Since Ang II-induced, KCl-induced and myogenic constriction of afferent arterioles require calcium entry through voltage-dependent calcium channels, the interaction between Rho/Rho-kinase and the calcium entry pathway may determine the afferent arteriolar tone induced by these stimuli.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Ken
authors.initials: K
authors.lastname: Okubo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanda
authors.forename: Shu
authors.initials: S
authors.lastname: Wakino
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000209:Acute-Phase Proteins / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology*; D054460:rho-Associated Kinases
chemical_list: D000209:Acute-Phase Proteins; D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C010781:acute-phase protein rho; D000804:Angiotensin II; C108830:Y 27632; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil