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Am J Physiol Regul Integr Comp Physiol (September 12, 2002). doi:10.1152/ajpregu.00336.2002
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Articles in PresS, published online ahead of print September 12, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00336.2002
Submitted on June 7, 2002
Accepted on September 8, 2002

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

Ulla C Kopp1*, Michael Z Cicha1, and Lori A Smith1

1 Departments of Internal Medicine & Pharmacology, Department of Veterans Affairs Medical Center and University of Iowa Roy J. and Lucille Carver College of Medicine, Iowa City, IA, USA

* To whom correspondence should be addressed. E-mail: ukopp{at}blue.weeg.uiowa.edu.

Increasing renal pelvic pressure results in PGE2-mediated release of substance P. Substance P increases afferent renal nerve activity (ARNA) which leads to a reflex increase in urinary sodium excretion (UNaV). Endogenous angiotensin (ANG) II modulates the responsiveness of renal mechanosensory nerves. The ARNA and UNaV 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 mm Hg were suppressed in CHF vs. sham-CHF rats fed normal sodium diet. In CHF rats, increasing renal pelvic pressure 2.5 and 7.5 mm Hg 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, PGE2 increased substance P release from 11±2 to 15±3 pg/min (NS) without and from 16±2 to 30±4 pg/min (P<0.01) with losartan in the incubation bath. Losartan had no effect on PGE2-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 PGE2-mediated release of substance P from renal pelvic nerves.




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