Renal and femoral vascular responses to endothelin-1 in dogs: role of prostaglandins.
Vascular responses to endothelin were examined with special reference to prostaglandins (PGs). Intrarenal infusion of endothelin (ET)-1 (1-5 ng/kg/min) to dogs caused a transient increase followed by a sustained decrease in renal blood flow, with no change in blood pressure or heart rate. Renal secretion rates of PGE2 and I2 (determined as 6-keto PGF1 alpha) were increased with ET, dose-dependently, and the intrarenal infusion of ET (5 ng/kg/min) elevated the systemic arterial concentration of 6-keto PGF1 alpha from 26 +/- 5 to 83 +/- 14 pg/ml. Because this increase in PG secretion was not affected by the platelet activating factor antagonist, CV 6209, it is unlikely that ET-induced renal PG production was platelet activating factor-mediated. Pretreatment with aspirin abolished completely the increased PG secretion elicited by ET and potentiated the ET-induced reduction renal blood flow. Intrafemoral infusion of ET (5 ng/kg/min) also induced an initial increase followed by a gradual decrease in femoral blood flow, without any increase in PG secretion from the hindlimb. Aspirin had no effects on the femoral hemodynamic action of ET. In addition, initial transient increases in either renal or femoral blood flow by endothelin were not affected by aspirin. Thus, the ET-induced production of renal PGs counteracts the renal vasoconstrictor action of ET, an event in marked contrast to the lack of any apparent involvement of PGs in the femoral hemodynamic action of ET. The ET-induced transient vasodilation shows no apparent relation to the cyclooxygenase products.
Miura
K
K
Department of Pharmacology, Osaka City University Medical School, Japan.
Yukimura
T
T
Yamashita
Y
Y
Shimmen
T
T
Okumura
M
M
Yamanaka
S
S
Imanishi
M
M
Yamamoto
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000096:biosynthesis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D010972:Platelet Activating Factor; D011453:Prostaglandins; D011726:Pyridinium Compounds; C053321:CV 6209; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D001241:Aspirin