RENAL NERVES AND THE NATRIURESIS FOLLOWING UNILATERAL RENAL EXCLUSION IN THE RAT

Both acute unilateral nephrectomy (AUN) and acute ureteral pressure elevation (UPE) stimulate sodium excretion (UNaV) from the contralateral kidney, a response which in each case is interrupted by prior denervation of either kidney. Yet the natriuresis after AUN is known to be related to an increase in the plasma concentration of a γ-melanocyte stimulating hormone (γ-MSH)-like peptide. In anesthetized rats, sham AUN had no effect on contralateral UNaV, and plasma immunoreactive (IR) γ-MSH concentration was 10.6 ± 3.0 (SD) fmol/ ml. In rats with intact renal innervation, UNaV more than doubled after AUN (P < 0.001), and IR-γ-MSH was increased to 14.9 ± 4.6 fmol/ml (P < 0.025). Unilateral renal denervation led to the expected increase in ipsilateral and decrease in contralateral UNaV, and neither sham AUN nor AUN of the denervated of innervated kidney influenced UNaV. In all three of these groups, IR-γ-MSH concentration was reduced below the sham or post-AUN values seen in rats with innervated kidneys, to 4.9 ± 3.3, 3.8 ± 3.4, and 2.8 ± 3.5 fmol/ml, respectively (P < 0.001 for all). These results suggested that removal of renal afferent nerve input by renal denervation lowered basal IR-γ-MSH activity and prevented the stimulated level normally seen after AUN. To examine the effect of stimulating afferent renal nerve activity, we carried out UPE, a maneuver known to increase ipsilateral afferent renal nerve traffic through activation of renal mechanoreceptors, as well as cause a natriuresis from the contralateral kidney. No change in UNaV occurred after sham UPE, and plasma IR-γ-MSH was 10.8 ± 3.9 fmol/ml. UPE caused UNaV to double, and IR-γ-MSH rose to 20.0 ± 7.3 fmol/ml (P < 0.002). This natriuresis was blocked in rats pretreated with anti-γ-MSH antiserum despite an equivalent increase in ureteral pressure. These observations indicate that afferent renal nerve activity is important in facilitating both basal and stimulated plasma IR-γ-MSH after AUN, and that activation of afferent traffic by UPE itself leads to an increase in the plasma concentration of this peptide. This increase is important in the contralateral natriuresis, since the latter is prevented by anti-γ-MSH antiserum. These studies thus define a new neurohumoral system involved in the regulation of UNaV.