EXCRETORY RESPONSES TO RENAL NERVE-STIMULATION DURING INHIBITION OF NEUTRAL METALLOENDOPEPTIDASE AND ANGIOTENSIN-CONVERTING ENZYME IN THE RAT

To evaluate the interaction between renal nerves, the atrial natriuret ic peptide (ANP), and the renin-angiotensin system (RAS), electrical s timulation of renal nerves was performed in spontaneously hypertensive rats (SHR) and in their normotensive controls, Wistar Kyoto rats (WKY ), before and after pharmacologic treatment with (a) a neutral endopep tidase inhibitor (NEP-i) to enhance the intrarenal ANP activity; (b) a n ACE inhibitor (ACE-i) to block RAS; (c) both NEP-i and ACE-i; and (d ) the vehicle of the drugs. Renal nerve stimulation did not change art erial pressure (AP) but reduced renal blood flow (RBF), glomerular fil tration rate (GFR), and urinary sodium excretion (UNa+V) in both WKY a nd SHR. NEP-i treatment in WKY and SHR had no systemic or renal hemody namic effects but increased GFR and urinary cyclic guanosine monophosp hate (GMP) excretion; UNa+V increased (+2.78 +/- 0.31 mu Eq/min) in WK Y, whereas it did not change in SHR (+0.83 +/- 0.79 mu Eq/min). In bot h strains, ACE-i treatment reduced AP, increased RBF, and did not chan ge GFR and UNa+V. The combined treatment with NEP-i and ACE-i did not modify the natriuretic effect observed in NEP-i-treated WKY (+4.29 +/- 1.25 mu Eq/min), but it elicited a natriuretic effect in SHR (+3.98 /- 1.29 mu Eq/min). Pharmacologic treatment did not change the hemodyn amic and excretory responses to renal nerve stimulation in both WKY an d SHR. In conclusion, NEP-i treatment increased UNa+V in normotensive rats without changing AP. In hypertensive rats, the natriuretic effect of NEP-i became evident only after block of RAS by ACE-i. Neither NEP -i nor ACE-i, even in combination, could modify the renal responses to sympathetic stimulation.