title: Regulation of intrarenal blood flow in experimental heart failure: role of endothelin and nitric oxide.
abstract: Congestive heart failure(CHF) is associated with a marked decrease in cortical blood flow and preservation of medullary blood flow. In the present study we tested the hypothesis that changes in the endothelin (ET) and nitric oxide (NO) systems in the kidney may contribute to the altered intrarenal hemodynamics in rats with aortocaval fistula, an experimental model of CHF. Cortical and medullary blood flow were measured simultaneously by laser-Doppler flowmetry in controls and rats with compensated and decompensated CHF. As previously reported [K. Gurbanov, I. Rubinstein, A. Hoffman, Z. Abassi, O. S. Better, and J. Winaver. Am. J Physiol. 271 (Renal Fluid Electrolyte Physiol. 40): F1166-F1172, 1996], administration of ET-1 in control rats produced a sustained cortical vasoconstriction and a transient medullary vasodilatory response. In rats with decompensated CHF, cortical vasoconstriction was severely blunted, whereas ET-1-induced medullary vasodilation was significantly prolonged. This prolonged response was mimicked by IRL-1620, a specific ETB agonist, and partially abolished by NO synthase (NOS) blockade. In line with these findings, expression of ET-1, ETA and ETB receptors, and endothelial NOS (eNOS), assessed by RT-PCR, and eNOS immunoreactivity, assessed by Western blotting, was significantly higher in the medulla than in the cortex. Moreover, expression of ET-1 mRNA in the cortex and eNOS mRNA in the cortex and the medulla increased in proportion to the severity of heart failure. These findings indicate that CHF is associated with altered regulation of intrarenal blood flow, which reflects alterations in expression and activity of the ET and NO systems. It is further suggested that exaggerated NO activity in the medulla contributes to preservation of medullary blood flow in the face of cortical vasoconstriction in CHF.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Abassi
authors.forename: K
authors.initials: K
authors.lastname: Gurbanov
authors.forename: I
authors.initials: I
authors.lastname: Rubinstein
authors.forename: O S
authors.initials: OS
authors.lastname: Better
authors.forename: A
authors.initials: A
authors.lastname: Hoffman
authors.forename: J
authors.initials: J
authors.lastname: Winaver
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000201:enzymology; D006333:Heart Failure / Q000503:physiopathology*; D007672:Kidney Cortex / Q000098:blood supply; D007679:Kidney Medulla / Q000098:blood supply; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000235:genetics; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D012333:RNA, Messenger; D017466:Receptors, Endothelin; C074308:sovateltide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase