Impaired Activation of Renal Sensory Nerves in Diabetes: Role of Angiotensin

Abstract

Hypertension, altered renal sodium handling, increased angiotensin (ANG) II activity and loss of sensory innervation are prevalent in diabetes mellitus (DM). In normal rats, afferent renal denervation results in salt sensitive hypertension showing a role for renal sensory nerves in sodium balance and arterial pressure. Activation of renal sensory nerves is impaired in streptozotocin (STZ)-treated rats (type I DM). Because high endogenous ANG II impairs renal sensory nerve activation, we examined if impaired renal sensory nerve activation in STZ rats is due to ANG II. In normal rats, activating renal sensory nerves by PGE2 increases renal pelvic release of substance P from 7.3±2.1 to 14.4±3.2 pg/min. PGE2 did not increase substance P release in STZ rats, from 4.7±0.7 to 5.8±0.7 pg/min (NS), but increased substance P release in insulin-treated STZ rats, from 4.6±0.5 to 12.1±1.1 pg/min. Adding losartan to the bath enhanced the PGE2-mediated release of substance P in STZ rats, from 5.4±1.0 to 9.7±1.5 pg/min. Losartan had no effect in insulin-treated STZ-rats or normal rats. In Zucker diabetic fatty (ZDF) obese rats (type II DM), PGE2 mediated substance P release was also impaired (P<0.01), from 10.9±1.1 to 16.9±1.4 pg/min compared to ZDF lean; from 10.2±0.9 to 21.5±1.4 pg/min. However, adding losartan to the bath had no effect on the PGE2-mediated substance P release in ZDF obese rats. In non-diabetic Zucker obese and lean rats, PGE2 increased substance P release to a similar extent as in normal rats. Conclusion; the responsiveness of renal sensory nerves is impaired in STZ and ZDF obese rats. The impaired renal sensory nerve activation is dependent on ANG II in STZ rats but not in ZDF obese rats.