title: 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.
authors.affiliation: Department of Internal Medicine, University of Iowa 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* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000294:innervation* / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism*; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism; D012982:Sodium, Dietary / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D013373:Substance P; D019808:Losartan; D015232:Dinoprostone