Beneficial influence of ketanserin on autoregulation of blood flow in post-ischemic kidneys.
The influence of ketanserin, a S2-serotonergic receptor blocker, on the impaired renal hemodynamics in a clamp model of renal ischemia in rats was investigated in this study. Serotonin-induced vasoconstriction of the renal vascular bed was augmented after ischemia. This constriction is blocked by ketanserin (0.05 mg/kg i.v. bolus, followed by 0.1 mg/kg per h infusion). The influence of the same ketanserin treatment on the response of RBF versus a stepwise lowering of the renal perfusion pressure was studied in post-ischemic kidneys with an established loss of autoregulation of RBF. An almost perfect restoration of the autoregulatory response was apparent after the S2-serotonergic antagonism. Despite this beneficial effect on renal hemodynamics, renal function, judged by measurement of GFR and urinary sodium excretion rate, was not influenced by an acute infusion of ketanserin in post-ischemic kidneys. It is suggested that serotonin plays a pivotal role in the suppression of autoregulation of RBF by a S2-serotonergic receptor-mediated vasoconstrictor effect in the post-ischemic kidney. It most likely masks the potential myogenic dilatory response of the smooth muscle cells in renal preglomerular microvasculature. Restoration of the renal autoregulatory capacity by S2-serotonergic receptor antagonism could be of clinical relevance in human post-ischemic acute renal failure.
Verbeke
M
M
Laboratory for Histology, University of Gent, Belgium.
Smöllich
B
B
van de Voorde
J
J
de Ridder
L
L
Lameire
N
N
D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007511:Ischemia / Q000503:physiopathology*; D007650:Ketanserin / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012964:Sodium / Q000652:urine
D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D012964:Sodium