Effects of A-192621.1, a specific endothelin-B antagonist, on intrarenal hemodynamic responses to endothelin-1.
The present study examined the effects of A-192621.1, a highly selective endothelin-B- (ETB) receptor antagonist, on the renal hemodynamic and systemic actions of endothelin-1 (ET-1). Intravenous injection of ET-1 (1.0 nmol/kg) into anesthetized rats produced a sustained decrease in renal blood flow (assessed by ultrasonic flowmeter) and a significant increase in renal vascular resistance, as well as an increase in mean arterial pressure. These changes were significantly augmented by pretreatment with A-192621.1 (3.0 mg/kg/h). Analysis of intrarenal blood flow by laser-Doppler flowmeter revealed that ET-1 caused a marked and sustained decrease in cortical blood flow, associated with a transient increase in medullary blood flow. The reduction in cortical blood flow in response to ET-1 was further enhanced by pretreatment with A-192621.1, whereas the ET-1-induced medullary vasodilatation was completely abolished and reversed into a vasoconstrictor response. These findings suggest that the ETB-receptors mediate the systemic and renal vasodilatory actions of ET-1 in the rat, and that their activation may serve as a physiological counterbalance that modulates ET-1-induced vasoconstriction.
Brodsky
S
S
Department of Physiology and Biophysics, Faculty of Medicine, Technion-Israel Institute of Technology, Rambam Medical Center Haifa.
Abassi
Z
Z
Wessale
J
J
Ramadan
R
R
Winaver
J
J
Hoffman
A
A
D000818:Animals; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance
C120508:A 192621; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin