Endogenous angiotensin modulates PGE(2)-mediated release of substance P from renal mechanosensory nerve fibers.

Abstract

Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) by a prostaglandin E2 (PGE2)-mediated release of substance P (SP) from renal pelvic sensory nerves. We examined whether the ARNA responses were modulated by high- and low-sodium diets. Increasing renal pelvic pressure resulted in greater ARNA responses in rats fed a high-sodium than in those fed a low-sodium diet. In rats fed a low-sodium diet, increasing renal pelvic pressure 2.5 and 7.5 mmHg increased ARNA 2 +/- 1 and 13 +/- 1% before and 12 +/- 1 and 22 +/- 2% during renal pelvic perfusion with 0.44 mM losartan. In rats fed a high-sodium diet, similar increases in renal pelvic pressure increased ARNA 10 +/- 1 and 23 +/- 3% before and 1 +/- 1 and 11 +/- 2% during pelvic perfusion with 15 nM ANG II. The PGE2-mediated release of SP from renal pelvic nerves in vitro was enhanced in rats fed a high-sodium diet and suppressed in rats fed a low-sodium diet. The PGE2 concentration required for SP release was 0.03, 0.14, and 3.5 microM in rats fed high-, normal-, and low-sodium diets. In rats fed a low-sodium diet, PGE2 increased renal pelvic SP release from 5 +/- 1 to 6 +/- 1 pg/min without and from 12 +/- 1 to 21 +/- 2 pg/min with losartan in the incubation bath. Losartan had no effect on SP release in rats fed normal- and high-sodium diets. ANG II modulates the responsiveness of renal pelvic mechanosensory nerves by inhibiting PGE2-mediated SP release from renal pelvic nerve fibers.