Renal effects of endothelin in anesthetized rabbits.
Intrarenal arterial infusion of endothelin-1 (1, 3 and 10 ng/kg per min) reduced renal blood flow, urine flow rate and urinary Na+ excretion without affecting fractional Na+ excretion in anesthetized rabbits. An endothelin ET(A) receptor antagonist (R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-me thyl-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl]amino-3-(2-pyr idyl)propionic acid (FR139317, 1 microg/kg per min) attenuated the endothelin-1 (1 ng/kg per min)-induced renal responses. An endothelin ET(B) receptor antagonist N-cis 2,6-dimetylpiperidinocarbonyl-L-gamma-metylleucyl-D-1-met hoxycarbonyltryptophanyl-D-norleucine (BQ-788, 1 microg/kg per min) potentiated the endothelin-1-induced changes in renal blood flow, urine flow rate and urinary Na+ excretion. A nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 50 microg/kg per min) also potentiated the endothelin-1-induced reductions in urine flow rate and urinary Na+ excretion but not the reduction in renal blood flow. Endothelin-1 reduced fractional Na+ excretion in the presence of BQ-788 or L-NAME. A spontaneous NO donor 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (30 ng/kg per min) slightly attenuated the antinatriuresis but not the vasoconstriction induced by endothelin-1. These results suggest that in the rabbit kidney in vivo endothelin ET(A) receptors mediate endothelin-1-evoked vasoconstriction and tubular Na+ reabsorption, that the concomitant stimulation of endothelin ET(B) receptors by endothelin-1 counteracts both the ET(A) receptor-mediated vascular and tubular actions, and that the tubular action, but not the vascular action, of endothelin-1 is also susceptible to changes in renal NO level.
Ono
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N
Department of Pharmacology, Pharmaceutical Institute, Tohoku University, Aobayama, Sendai, Japan.
Matsui
T
T
Yoshida
M
M
Suzuki-Kusaba
M
M
Hisa
H
H
Satoh
S
S
D000704:Analysis of Variance; D000758:Anesthesia; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014554:Urination / Q000187:drug effects
C115239:3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine; D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006834:Hydrazines; D007211:Indoles; D020030:Nitric Oxide Donors; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C079574:FR 139317; C086539:BQ 788; D012964:Sodium; D019331:NG-Nitroarginine Methyl Ester