Bilateral kidney ligation abolishes pressor response to N-G-nitro-D-arginine

We have shown that N-G-nitro-D-arginine (D-NNA) is 50% as potent as N-G-nit ro-L-arginine (L-NNA) in causing presser response and 2-3% as potent as L-N NA in inhibiting endothelium-dependent relaxation in vitro. These results s uggest in vivo activation of D-NNA. Furthermore, the potency of D-NNA was m arkedly increased after it had been incubated with homogenate of the kidney , but not plasma or homogenate of the aorta, lungs or liver. This study exa mined if bilateral ligation of the kidneys attenuated the biological action of D-NNA. I.v. bolus of D-NNA (16 mg/kg), L-NNA (3 mg/kg) and norepinephri ne (0.25-16 mu g/kg) increased arterial pressure in sham-operated rats. Bil ateral ligation of the kidneys abolished presser response to D-NNA, but not L-NNA and norepinephrine. I.v. bolus D-NNA in sham-operated rats, but not kidney-ligated rats, inhibited relaxation response to acetylcholine in pre- constricted aortic rings ex vivo. These results indicate that the kidney is the primary organ which activates D-NNA. (C) 1999 Elsevier Science B.V. Al l rights reserved.