title: Effect of renal injury-induced neurogenic hypertension on NO synthase, caveolin-1, AKt, calmodulin and soluble guanylate cyclase expressions in the kidney.
abstract: Single injection of a small quantity of phenol into the cortex of one kidney in rats results in development of persistent hypertension (HTN) which is thought to be mediated by activation of renal afferent and efferent sympathetic pathways and sodium retention. Nitric oxide (NO) plays a major role in regulation of renal vascular resistance, tubular Na(+) reabsorption, pressure natriuresis, and thereby systemic arterial pressure. The present study was performed to test the hypothesis that chronic renal injury-induced HTN may be associated with dysregulation of NO system in the kidney. Accordingly, urinary NO metabolite (NO(x)) and cGMP excretions as well as renal cortical tissue (right kidney) expressions of NO synthase (NOS) isoforms [endothelial, neuronal, and inducible NOS, respectively (eNOS, nNOS, and iNOS)], NOS-regulatory factors (Caveolin-1, phospho-AKt, and calmodulin), and second-messenger system (soluble guanylate cyclase [sGC] and phosphodiesterase-5 [PDE-5]) were determined in male Sprague-Dawley rats 4 wk after injection of phenol (50 mul of 10% phenol) or saline into the lower pole of left kidney. The phenol-injected group exhibited a significant elevation of arterial pressure, marked reductions of urinary NO(x) and cGMP excretions, downregulations of renal tissue nNOS, eNOS, Phospho-eNOS, iNOS, and alpha chain of sGC. However, renal tissue AKt, phospho-AKT, Calmodulin, and PDE-5 proteins were unchanged in the phenol-injected animals. In conclusion, renal injury in this model results in significant downregulations of NOS isoforms and sGC and consequent reductions of NO production and cGMP generation by the kidney, events that may contribute to maintenance of HTN in this model.
authors.affiliation: Division of Nephrology and Hypertension, University of California, Irvine, CA 92868, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Bai
authors.forename: S
authors.initials: S
authors.lastname: Ye
authors.forename: R
authors.initials: R
authors.lastname: Mortazavi
authors.forename: V
authors.initials: V
authors.lastname: Campese
authors.forename: N D
authors.initials: ND
authors.lastname: Vaziri
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002147:Calmodulin / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D006152:Cyclic GMP / Q000652:urine; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006162:Guanylate Cyclase / Q000378:metabolism*; D006973:Hypertension / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000652:urine; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D019800:Phenol / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase
chemical_list: D002147:Calmodulin; D051242:Caveolin 1; D007527:Isoenzymes; D009566:Nitrates; D018160:Receptors, Cytoplasmic and Nuclear; D019800:Phenol; D003404:Creatinine; D019001:Nitric Oxide Synthase; D051057:Proto-Oncogene Proteins c-akt; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP