NITRIC-OXIDE INHIBITION IN RATS IMPROVES BLOOD-PRESSURE AND RENAL-FUNCTION DURING HYPOVOLEMIC SHOCK

We have examined the systemic and renal hemodynamic effects of nitric oxide (NO) inhibition with N(G)-monomethyl-L-arginine (L-NMMA) in normotensive rats as well as in rats with hypovolemic shock induced by hemorrhage. L-NMMA increased mean arterial blood pressure (MAP) from 114 +/- 4 to 130 +/- 6 mmHg (P < 0.05) in the nonhemorrhaged rats and from 61 +/- 3 to 89 +/- 3 mmHg (P < 0.05) in the hypovolemic animals. The absolute increase in MAP was greater in the hypovolemic (31 +/- 3 mmHg) than in the nonhemorrhaged (15 +/- 2 mmHg) rats (P < 0.05). An excess of L-arginine reversed the increase in MAP induced by L-NMMA in both groups. In the normotensive rats the increase in blood pressure was associated with an elevation in renal vascular resistance (RVR; from 6.5 +/- 0.7 to 8.2 +/- 0.9 mmHg.ml-1. min-1, P < 0.05) so that renal plasma flow (RPF) and glomerular filtration rate (GFR) were unchanged. In contrast, in the hypotensive rats, the marked increase in MAP induced by L-NMMA infusion was not associated with a significant increase in RVR. As a result L-NMMA increased both RPF (from 6.0 +/- 0.4 to 7.8 +/- 0.4 ml/min, P < 0.05) as well as GFR (from 1.7 +/- 0.2 to 2.5 +/- 0.2 ml/min, P < 0.05). We conclude that NO is produced and modulates peripheral resistance in normotensive rats as well as in rats with hypovolemic shock. In the hypovolemic rats NO inhibition substantially improves RPF and GFR. Thus NO production contributes to the hypotension and reduced renal function in hypovolemic rats by maintaining peripheral vasodilation.