ROLE OF EICOSANOIDS IN RENAL ANGIOTENSIN-II VASOCONSTRICTION DURING NITRIC-OXIDE BLOCKADE

Nitric oxide (NO) buffers the effect of vasoconstrictors currently act ive in the renovascular system. Enhancement of the angiotensin II (Ang II)-induced vasoconstriction during NO blockade comprises both AT(2)- sensiiive potentiation, decreasing the half maximal vasoconstriction ( EC50) value to the subnanomolar concentration range, and augmentation, increasing the maximal effect (E-max) value in the isolated perfused rat kidney. In this study, we examine whether constrictory prostanoids are involved in Ang II subtype receptor (AT(2))-sensitive potentiatio n of the Ang II effect during NO blockade. Thus, Ang II-induced vasoco nstriction (0.1 or 10 nM Ang II) was measured in six series of constan t-flow perfused isolated rat kidneys in the presence of indomethacin u nder control conditions, during NO inhibition, and during combined inh ibition of NO and all arachidonic pathways by eicosatetraynoic acid (E TYA), 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 n M Ang II increased about 20-fold during NO inhibition, reflecting main ly potentiation of the Ang II effect. This increase was abrogated by E TYA. We conclude that vasoconstrictor eicosanoids, which are suppresse d by endogenous NO, mediate AT(2)-sensitive potentiation of the Ang II -induced vasoconstriction in the rat kidney.