Impaired responsiveness of renal mechanosensory nerves in heart failure: role of endogenous angiotensin.

Increasing renal pelvic pressure results in PGE(2)-mediated release of substance P. Substance P increases afferent renal nerve activity (ARNA), which leads to a reflex increase in urinary sodium excretion (U(Na)V). Endogenous ANG II modulates the responsiveness of renal mechanosensory nerves. The ARNA and U(Na)V responses are suppressed by low- and enhanced by high-sodium diet. We examined whether the ARNA responses are altered in rats with congestive heart failure (CHF), a condition characterized by increased ANG II and sodium retention. The ARNA responses to increasing renal pelvic pressure </=7.5 mmHg were suppressed in CHF vs. sham-CHF rats fed normal sodium diet. In CHF rats, increasing renal pelvic pressure 2.5 and 7.5 mmHg increased ARNA 0 +/- 1 and 13 +/- 2% (P < 0.01) before and 9 +/- 1 (P < 0.01) and 19 +/- 1% (P < 0.01) during renal pelvic perfusion with losartan. Losartan had no effect on the ARNA responses in sham-CHF rats. In isolated renal pelvises from CHF rats, PGE(2) increased substance P release from 11 +/- 2 to 15 +/- 3 pg/min (not significant) without and from 16 +/- 2 to 30 +/- 4 pg/min (P < 0.01) with losartan in the incubation bath. Losartan had no effect on PGE(2)-mediated substance P release in sham-CHF rats. In conclusion, the responsiveness of renal mechanosensory nerves is impaired in CHF rats due to ANG II inhibiting PGE(2)-mediated release of substance P from renal pelvic nerves.