Impaired responsiveness of renal sensory nerves in streptozotocin-treated rats and obese Zucker diabetic fatty rats: role of angiotensin.
Increasing afferent renal nerve activity decreases efferent renal nerve activity and increases urinary sodium excretion. Activation of renal pelvic mechanosensory nerves is impaired in streptozotocin (STZ)-treated rats (model of type 1 diabetes). Decreased activation of renal sensory nerves would lead to increased efferent renal nerve activity, sodium retention, and hypertension. We examined whether the reduced activation of renal sensory nerves in STZ rats was due to increased renal angiotensin activity and whether activation of the renal sensory nerves was impaired in obese Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). In an isolated renal pelvic wall preparation from rats treated with STZ for 2 wk, PGE2 failed to increase the release of substance P, from 5 +/- 1 to 6 +/- 1 pg/min. In pelvises from sham STZ rats, PGE2 increased substance P release from 6 +/- 1 to 13 +/- 2 pg/min. Adding losartan to the incubation bath increased PGE2-mediated release of substance P in STZ rats, from 5 +/- 1 to 10 +/- 2 pg/min, but had no effect in sham STZ rats. In pelvises from obese ZDF rats (22-46 wk old), PGE2 increased substance P release from 12.0 +/- 1.2 to 18.3 +/- 1.2 pg/min, which was less than that from lean ZDF rats (10.3 +/- 1.6 to 22.5 +/- 2.4 pg/min). Losartan had no effect on the PGE2-mediated substance P release in obese or lean ZDF rats. We conclude that the mechanisms involved in the decreased responsiveness of the renal sensory nerves in STZ rats involve activation of the renin angiotensin system in STZ but not in obese ZDF rats.
Kopp
Ulla C
UC
Department of Internal Medicine, Department of Veterans Affairs Medical Center, Bldg. 41, Rm 124, Highway 6W, Iowa City, IA 52246, USA. ulla-kopp@uiowa.edu
Cicha
Michael Z
MZ
Yorek
Mark A
MA
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000809:Angiotensins / Q000502:physiology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D015232:Dinoprostone / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009765:Obesity / Q000235:genetics / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D013373:Substance P / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000809:Angiotensins; D013373:Substance P; D019808:Losartan; D015232:Dinoprostone; D002211:Capsaicin