title: Renal functional responses in diabetic nephropathy following chronic bilateral renal denervation.
abstract: Renal innervation operates in conjunction with the intrarenal renin-angiotensin system (RAS) to control tubular reabsorption of sodium and water. This relationship remains unexplored in diabetic nephropathy. This study investigates the effects of acute RAS inhibition and chronic renal denervation on renal function in diabetic rats. Diabetes was induced in mRen-2 rats prior to conducting chronic bilateral denervation in diabetic and normoglycaemic animals. At 12-weeks post-diabetic induction, renal haemodynamics and tubular handling of sodium and water were measured before and after acute captopril infusion. Neither GFR nor renal blood flow were affected by diabetes or chronic renal denervation alone. While captopril produced natriuretic and diuretic responses in chronically-denervated diabetic animals, shown by increases (P<0.05) of 38±14% in absolute (UNaV), and 71±20% in fractional sodium excretion (FENa), and 68±17% in urine volume (UV); in the innervated-diabetic group captopril produced anti-natriuretic effects (UNaV and FENareduced by 41±10% and 29±13%, respectively; all P<0.05). This difference was not observed however in normoglycaemic groups where RAS inhibition produced anti-natriuretic (normoglycaemic denervated vs. innervated: 56±14% vs. 49±14% UNaV; 45±13% vs. 37±14% FENa) and anti-diuretic (normoglycaemic-denervated vs. innervated: 34±8% vs. 38±10% UV) effects in both denervated and innervated animals. These data indicate that renal neuronal control is altered in chronic hyperglycaemia. The role of the RAS in sodium conservation in the diabetic kidney, appears to be more significant in the absence of renal innervation, suggesting that the interaction between the RAS and renal sympathetic nervous system is responsible for changes in renal function in diabetic nephropathy.
authors.affiliation: Departments of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Physiology, University of Otago, Dunedin, New Zealand.
authors.forename: Gerard
authors.initials: G
authors.lastname: Davis
authors.affiliation: Departments of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Harrison
authors.affiliation: Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Walker
authors.affiliation: Departments of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand. Electronic address: ivan.sammut@otago.ac.nz.
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Sammut
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D003714:Denervation; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*; D045283:Natriuretic Agents / Q000494:pharmacology; D011897:Random Allocation; D055647:Rats, Transgenic; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D045283:Natriuretic Agents; D002216:Captopril