INTERACTIONS BETWEEN NITRIC-OXIDE AND PROSTANOIDS IN ISOLATED-PERFUSED KIDNEYS OF THE RAT

1 The present study was aimed to assess the interaction between nitric oxide (NO) and thromboxane (Tx) A(2)-prostaglandin (PG) H-2 in single -pass perfused isolated kidneys of the rat. 2 Noradrenaline (NA, 63 an d 110 nM) dose-dependently elevated the renal vascular resistance (RVR ), the giomerular filtration rate (GFR) and the urinary excretion of s odium (UNaV). Infusion of N-omega-nitro-L-arginine methyl ester (L-NAM E, 100 mu M), an inhibitor of NO synthesis, enhanced the effects of NA on RVR and on UNaV, but decreased those on GFR. The TxA(2)-PGH(2) (TP ) receptor blockade by GR32191B (10 mu M) attenuated this potentiating effect of L-NAME. 3 When renal perfusion pressure was stepwise increa sed from 90 to 150 mmHg, L-NAME similarly decreased renal perfusion fl ow rate and GFR. 4 The venous excretion of TxB(2) and 6-keto-PGF(1 alp ha) was increased by L-NAME in baseline conditions as well as after NA or increasing renal perfusion pressure (RPP). 5 These results suggest that: (1) TxA(2) and PGH(2) play an important role in the overall eff ect of the renal prostanoids, (2) NO strongly interacts with the cyclo -oxygenase pathway and reduces the prostanoid synthesis in the kidney, and (3) the presser effect of L-NAME partly relies upon the vasoconst rictor effect of TxA(2) and PGH(2).