INHIBITION OF NITRIC-OXIDE CAUSES EXAGGERATED NATRIURESIS IN SPONTANEOUSLY HYPERTENSIVE RATS

Competitive inhibition of the conversion of L-arginine to nitric oxide by a high dose of N-G-monomethyl-L-arginine (L-NMMA) leads to significant increases in arterial pressure, natriuresis, and diuresis in Sprague-Dawley rats. The purpose of this study was to determine the extent of the natriuretic and diuretic responses and the possible role of arterial pressure and renal interstitial hydrostatic pressure (RIHP) elevations with the infusion of L-NMMA in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Intravenous infusion of L-NMMA (15 mg/kg bolus followed by 500 mu g . kg(-1) . min(-1) continuous infusion) in WKY rats (n = 8) resulted in a significant increase in mean arterial pressure (MAP, 122 +/- 3 to 152 +/- 2 mmHg), RIHP (4.7 +/- 0.4 to 6.7 +/- 0.5 mmHg), fractional excretion of sodium (FE(Na), 0.76 +/- 0.21 to 4.74 +/- 0.70%), and urine flow rate (V, 27.7 +/- 5.0 to 161.3 +/- 19.6 mu l/min). Increases in RIHP and sodium and water excretions are abolished when renal perfusion pressure is prevented from increasing with L-NMMA infusion in a group of WKY rats (n = 6). In SHR (n = 6) administration of the same dose of L-NMMA resulted in no significant changes in MAP (172 +/- 3 to 178 +/- 2 mmHg) or RIHP (3.3 +/- 0.4 to 3.5 +/- 0.6 mmHg), but significantly higher increases in FE(Na) (1.19 +/- 0.26 to 7.52 +/- 0.68%) and V (47.1 +/- 10.0 to 248.3 +/- 25.7 mu l/min) compared with WKY rat. Changes in MAP and RIHP were significantly higher in WKY rat, whereas changes in sodium and water excretion were significantly higher in SHR in response to the same high dose of L-NMMA infusion. Fractional excretion of phosphate rose significantly with L-NMMA infusion in SHR, suggesting decreased proximal tubular reabsorption. Plasma levels of atrial natriuretic factor and endothelin-1 were unaffected by the infusion of L-NMMA. In conclusion, natriuretic and diuretic responses of SHR to the above dose of L-NMMA are exaggerated compared with those of WKY rat and are independent of significant alterations in MAP.