THE ROLE OF INTRARENAL NITRIC OXIDE IN THE NATRIURETIC RESPONSE TO DOPAMINE-RECEPTOR ACTIVATION

Abstract

Dopamine and dopamine-1 receptor agonists produce diuresis and natriuresis by causing changes in renal hemodynamics and by the activation of dopamine-1 receptors located within the various regions of the nephron. Nitric oxide plays an important role in the maintenance of systemic and regional hemodynamics. The present study was undertaken to investigate the effect of locally generated nitric oxide on renal function and its potential influence on the renal responses to dopamine-1 receptor agonists. The intrarenal infusion of a nitric oxide synthase inhibitor, L-NAME, (50 μg/kg min for 90 min) in anesthetized rats produced significant decreases in urine volume, urinary sodium excretion, glomerular filtration rate and fractional sodium excretion. These changes in renal function were associated with a concomitant decrease in urinary nitrate excretion, an indicator of nitric oxide release. However, L-NAME at this dose did not produce any significant changes in mean arterial pressure or heart rate. Intravenous infusion of fenoldopam (1 μg/kg min for 30 min), a selective dopamine-1 receptor agonist, produced diuresis and natriuresis without causing any changes in mean arterial pressure and heart rate. These renal effects of fenoldopam were significantly attenuated in animals that received the simultaneous infusion of L-NAME (intrarenal). Similar results were obtained with dopamine in that the natriuretic and diuretic response to dopamine was also attenuated during simultaneous infusion of dopamine with L-NAME. In addition, the diuresis and natriuresis produced by fenoldopam and dopamine was associated with increases in urinary nitrate excretion. Interestingly, these increases in the nitrate levels seen with fenoldopam and dopamine were also significantly reduced in the presence of L-NAME. These results indicate that intrarenal nitric oxide plays an important role in regulating renal sodium excretion and that an intact renal nitric oxide system is required for the full expression of diuretic and natriuretic response seen during dopamine-1 receptor activation.