Vasoconstrictor and vasodilator effects of serotonin in the isolated rabbit kidney.
The renal vascular effects of serotonin (5-HT) in vivo vary among preparations, which may reflect that this autacoid can modulate the vascular response to certain spasmogens. We investigated this phenomenon in the isolated rabbit kidney perfused under constant flow (5 ml/min) with Krebs-bicarbonate buffer. Dose-response experiments to 5-HT were conducted before and during an infusion of half-maximal effective doses of norepinephrine (NE), phenylephrine (PE) or endothelin-1 (ET-1). Each infusion was varied to raise the perfusion pressure (PP) from a baseline of 18-28 mm Hg to a level of 80-100 mm Hg. In the absence of infused NE, PE or ET-1, bolus injections of 5-HT had little or no effect. However, in the presence of NE, 5-HT injections of 20 pmol to 20 nmol caused a dose-dependent increase in PP; higher doses (0.4-4 mumol) of 5-HT caused a dose-dependent decrease in PP. Similar results with 5-HT were obtained in the presence of an infusion of PE. However, in the presence of ET-1, 5-HT injections elicited only a modest increase in PP, which was significantly less than the increase in the presence of NE; and they did not have the vasodilator effect on the isolated perfused kidney. Histamine injections only increased but did not decrease the PP in PE-precontracted renal vasculature. Infusion of 5-HT at 20 nmol/min potentiated the dose-dependent effect of NE on PP, but 5-HT infusion of 1 mumol/min attenuated the effect of NE on PP.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
T
T
Dept. of Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut.
Croce
K
K
Winquist
R J
RJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D010656:Phenylephrine; D012701:Serotonin; D009638:Norepinephrine