title: Rho-kinase contributes to pressure-induced constriction of renal microvessels.
abstract: Renal afferent arterioles (AFF) regulate glomerular capillary pressure through two main mechanisms: the myogenic response (MYO) and tubuloglomerular feedback (TGF). Because Rho-kinase and nitric oxide synthase (NOS) are established factors that modulate vascular tone, we examined the role of these factors in pressure-induced AFF tone in Wistar-Kyoto rats and in spontaneously hypertensive rats (SHR) using an intravital CCD camera. Elevated renal perfusion pressure elicited marked AFF constriction that was partially inhibited by gadolinium, furosemide and fasudil, which inhibit MYO, TGF and Rho-kinase, respectively; however, this AFF constriction was completely blocked by combined treatment with fasudil+gadolinium or fasudil+furosemide. S-methyl-L-thiocitrulline (SMTC) partially reversed the fasudil-induced inhibition of TGF-mediated, but not that of MYO-mediated, AFF constriction. In SHR, the pressure-induced AFF response was enhanced, and MYO- and TGF-induced constriction were exaggerated. In the presence of gadolinium, SMTC partially mitigated the fasudil-induced inhibition of TGF-mediated AFF constriction. Immunoblot analyses demonstrated that both Rho-kinase activity and neuronal NOS were augmented in SHR kidneys. In conclusion, Rho-kinase contributes to MYO- and TGF-mediated AFF responses, and these responses are enhanced in SHR. Furthermore, neuronal NOS-induced nitric oxide modulates the TGF mechanism. This mechanism constitutes a target for Rho-kinase in TGF-mediated AFF constriction.
authors.affiliation: Departments of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Homma
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Shu
authors.initials: S
authors.lastname: Wakino
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tokuyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanda
authors.forename: Satoru
authors.initials: S
authors.lastname: Tatematsu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Seitaro
authors.initials: S
authors.lastname: Fujishima
authors.forename: Shingo
authors.initials: S
authors.lastname: Hori
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D001160:Arterioles / Q000473:pathology; D001794:Blood Pressure; D002196:Capillaries; D002956:Citrulline / Q000008:administration & dosage / Q000031:analogs & derivatives; D005665:Furosemide / Q000008:administration & dosage; D005682:Gadolinium / Q000008:administration & dosage; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D007678:Kidney Glomerulus / Q000098:blood supply; D008297:Male; D008833:Microcirculation; D024510:Muscle Development; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives; D054460:rho-Associated Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D002956:Citrulline; D009569:Nitric Oxide; D005665:Furosemide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D005682:Gadolinium; D019001:Nitric Oxide Synthase; D054460:rho-Associated Kinases; D013890:Thiourea; C086717:S-methylthiocitrulline; C049347:fasudil