INDUCIBLE NITRIC-OXIDE SYNTHASE AND BLOOD-PRESSURE

In the present studies, the influence of inducible nitric oxide syntha se (NOS) inhibition with aminoguanidine on renal function and blood pr essure was examined in rats. Intravenous aminoguanidine infusion (60 m g . kg(-1) . hr(-1)) for 40 minutes to anesthetized Sprague-Dawley rat s (n=7) resulted in no significant changes in mean arterial pressure o r renal cortical blood now, while medullary-blood now was slightly inc reased. Despite minimal effects on renal blood now, urine now was sign ificantly decreased from 14.2+/-2.7 to 10.4+/-2.3 mu L . min(-1) . g k idney wt(-1) during aminoguanidine infusion. To examine the possible e ffects of inducible NOS on blood pressure, aminoguanidine (10 mg . kg( -1) . h(-1) IV) was infused chronically into uninephrectomized rats ma intained on a high salt (4.0% NaCl) diet. Mean arterial pressure signi ficantly increased from 104+/-2 to 118+/-3 mm Hg after 6 days of amino guanidine infusion (n=7) and returned to levels not different from tho se in the control group after 2 days of postcontrol infusion. Calcium- independent NOS activity in the renal medulla, a tissue that expresses inducible NOS in normal rats, was significantly decreased by 49% in t he aminoguanidine-infused group (n=6) compared with that activity in t he vehicle-infused control animals (n=6). In contrast, calcium-depende nt NOS activity in the renal medulla was not significantly altered by aminoguanidine infusion, indicating specificity of aminoguanidine for inducible NOS in these experiments. In a final group of rats (n=5), or al L-arginine administration in drinking water (2% wt/vol) increased p lasma arginine levels from 118+/-5 to 232+/-16 mu mol/L and blocked th e increase in arterial pressure after 6 days of aminoguanidine infusio n. The present experiments provide evidence supporting a role for indu cible NOS in the control of arterial pressure, possibly by renal tubul ar effects.