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 and 110 nM) dose-dependently elevated the renal vascular resistance (RVR), the giomerular filtration rate (GFR) and the urinary excretion of sodium (UNaV). Infusion of N-omega-nitro-L-arginine methyl ester (L-NAME, 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 increased from 90 to 150 mmHg, L-NAME similarly decreased renal perfusion flow rate and GFR. 4 The venous excretion of TxB(2) and 6-keto-PGF(1 alpha) 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 effect 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 vasoconstrictor effect of TxA(2) and PGH(2).