Relative preservation of the responsiveness to endothelin-1 during reperfusion following renal ischemia in the rat.
Reperfusion after renal ischemia is characterized by a preglomerular vasoconstriction. As endothelin-1 (ET-1) is a potent preglomerular vasoconstrictor, we designed a study to investigate the role of ET-1 in postischemic renal vasoconstriction. Renal ischemia was induced by 45 min of left renal artery clamping in anesthetized rats. After ischemia, renal blood flow was restored to only 61 +/- 4% of its preischemic value. The sensitivity to exogenous ET-1 after renal ischemia was decreased, but much less than the sensitivity to angiotensin II, which almost lost its vasoconstrictor effect, and to norepinephrine, which became a vasodilator. In addition, the binding affinity of [125I]ET-1 in the kidney increased significantly after renal ischemia, despite no change in the density of binding sites. These findings may be in favor of a role of endogenous ET-1 in postischemic renal vasoconstriction.
Clozel
M
M
Department of Pharmaceutical Research/Cardiovascular Diseases, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Löffler
B M
BM
Gloor
H
H
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D016232:Endothelins; D007457:Iodine Radioisotopes; D000804:Angiotensin II; D009638:Norepinephrine