title: Impaired responsiveness of renal mechanosensory nerves in heart failure: role of endogenous angiotensin.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Department of Veterans Affairs Medical Center, and University of Iowa Roy J. and Lucille Carver College of Medicine, Iowa City, Iowa 52242, USA. ukopp@blue.weeg.uiowa.edu
authors.forename: Ulla C
authors.initials: UC
authors.lastname: Kopp
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Cicha
authors.forename: Lori A
authors.initials: LA
authors.lastname: Smith
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D015232:Dinoprostone / Q000502:physiology; D006333:Heart Failure / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D009318:Natriuresis / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D011312:Pressure; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000494:pharmacology; D013373:Substance P / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000804:Angiotensin II; D013373:Substance P; D012964:Sodium; D019808:Losartan; D015232:Dinoprostone