Differential regulation of renal regional blood flow by endothelin-1.
The present study evaluated the effects and mechanisms of action of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively). CBF and MBF were measured simultaneously by laser-Doppler flowmetry in anesthetized male Wistar rats. Bolus injection of ET-1 (1.0 nmol/kg iv) produced a sustained decrease in CBF (delta = -30%) and a transient increase in MBF (delta = +35%). The medullary vasodilation induced by ET-1 was observed with doses lower than that required to produce cortical vasoconstriction; was completely blocked by bosentan, a mixed ETA/B-receptor antagonist; and was mimicked by IRL-1620, a specific ETB-receptor agonist. In contrast, BQ-123, an ETA-receptor antagonist, failed to inhibit the ET-1-dependent medullary vasodilation but effectively blocked the cortical vasoconstriction induced by the peptide. Finally, inhibition of nitric oxide (NO) synthase completely abolished, whereas cylooxygenase inhibition attenuated, the effect of ET-1 on MBF. The data demonstrate that ET-1 exerts opposite effects on renal cortical and medullary circulation, i.e., ETA-receptor-mediated cortical vasoconstriction and ETB-mediated medullary vasodilation. Furthermore, the medullary vasodilation induced by ET-1 is dependent on the NO system and, to a lesser extent, on prostaglandin generation.
Gurbanov
K
K
Department of Physiology and Biophysics, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Rubinstein
I
I
Hoffman
A
A
Abassi
Z
Z
Better
O S
OS
Winaver
J
J
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D019332:Endothelin-1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007672:Kidney Cortex / Q000098:blood supply; D007679:Kidney Medulla / Q000098:blood supply; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester