Role of eicosanoids in renal angiotensin II vasoconstriction during nitric oxide blockade.
Nitric oxide (NO) buffers the effect of vasoconstrictors currently active in the renovascular system. Enhancement of the angiotensin II (Ang II)-induced vasoconstriction during NO blockade comprises both AT2-sensitive potentiation, decreasing the half maximal vasoconstriction (EC50) value to the subnanomolar concentration range, and augmentation, increasing the maximal effect (Emax) value in the isolated perfused rat kidney. In this study, we examine whether constrictory prostanoids are involved in Ang II subtype receptor (AT2)-sensitive potentiation of the Ang II effect during NO blockade. Thus, Ang II-induced vasoconstriction (0.1 or 10 nM Ang II) was measured in six series of constant-flow perfused isolated rat kidneys in the presence of indomethacin under control conditions, during NO inhibition, and during combined inhibition of NO and all arachidonic pathways by eicosatetraynoic acid (ETYA), an analog of arachidonic acid. The vasoconstriction elicited by 10 nM Ang II, which is the maximal response, increased about threefold during NO inhibition compared with control. This augmentation was not affected by ETYA. In contrast, the vasoconstriction elicited by 0.1 nM Ang II increased about 20-fold during NO inhibition, reflecting mainly potentiation of the Ang II effect. This increase was abrogated by ETYA. We conclude that vasoconstrictor eicosanoids, which are suppressed by endogenous NO, mediate AT2-sensitive potentiation of the Ang II-induced vasoconstriction in the rat kidney.
Muller
C
C
Pharmacology Department, University Louis Pasteur School of Medicine, Strasbourg, France.
Endlich
K
K
Helwig
J J
JJ
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D015777:Eicosanoids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000737:chemistry / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009924:Organ Culture Techniques; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000502:physiology*
D015777:Eicosanoids; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D000804:Angiotensin II; D015117:5,8,11,14-Eicosatetraynoic Acid; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester