Low-dose nitric oxide inhibition produces a negative sodium balance in conscious dogs

Nitric oxide modulates renal hemodynamics and salt and water handling. Stud ies on the latter have provided conflicting results, however. Electrolyte a nd water balances were therefore studied in 28 beagles for 4 d, to determin e the various effects of nitric oxide synthase (NOS) inhibition on renal fu nction. The dogs were chronically equipped with aortic occluders to reduce renal perfusion pressure (RPP), bladder catheters, and catheters for measur ements of RPP and mean arterial BP. A swivel system allowed free movement w ithin the kennels. In a first set of experiments, a nonpressor dose of L-N omega -nitroarginine (LN) (3 mug/min per kg body wt) was administered, to p revent increases in mean arterial BP and thus pressure effects on renin rel ease and natriuresis. Remarkably, the nonpressor dose of LN caused a negati ve sodium balance. The natriuretic effect may involve reduced plasma renin activity, reduced aldosterone concentrations, and increased atrial natriure tic peptide concentrations. Changes in aldosterone levels, however, were th e only parameters to parallel the time course of sodium excretion. In a sec ond set of experiments, a sodium-retaining challenge was elicited by reduct ion of RPP. Dogs without NOS inhibition escaped sodium retention during RPP reduction after 2 d ("pressure escape"). LN neither ameliorated nor aggrav ated the sodium-retaining effect of reduced RPP, nor did it compromise the accomplishment of pressure escape. In conclusion, inhibition of NOS with a low dose of LN results in a reduction of total-body sodium. This effect mai nly relies on reduced aldosterone concentrations. Furthermore, LN does not change the regulatory response to long-term RPP reduction.