Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats

Background. Renal insufficiency develops in diabetes and shows structural a nd functional abnormalities. Renal afferents, including chemoreceptors and mechanoreceptors located in the vascular and ureteropelvic portions of the kidney, may reflect changes in the environment and trigger an afferent nerv e-mediated regulatory function that is known as the reno renal reflex. In t his study, the involvement of these renal sensory receptors during the earl y diabetic state is defined. Methods. Diabetes was induced in rats after a tail vein injection of strept ozotocin (STZ; 60 mg/kg intravenously). Four groups of rats, control (C), d iabetic (DM), diabetic with acute insulin treatment (DMAI, 9 U/rat, subcuta neously, on the experimental day), and chronic insulin treatment (DMCI, 9 U i rat, subcutaneously, daily) were studied. Spontaneous firing type 2-renal chemoreceptor (CR2), arterial mechanoreceptor (MRa), ureteropelvic mechano receptor (MRu), and venous mechanoreceptor (MRv) were identified by single- unit analysis of renal efferent nervous activity. The receptor activities w ere confirmed by their response patterns to stimuli elicited by renal arter ial occlusion (RAO), backflow of urine, increasing arterial pressure, incre asing ureteropelvic pressure (UP), or renal venous occlusion (RVO). The res ponse of these afferent receptors to a challenge of volume expansion and th eir functional activities on renorenal reflexes were also examined. Immunos taining with PGP 9.5 was applied for examination of the nerve distribution in the diabetic kidney. The tissue level of histamine in the renal pelvis w as determined. We explored the effect of histamine on renal receptor activi ty in these animals to address the possible role of histamine in MRu recept or activity. Results. In early diabetics, signaling activities in MRa and MRv were maint ained; however, activity in CR2 and MRu was depressed. For CR2, the reduced basal discharge and the repressed responses to RAG, backflow of urine, and volume expansion found in DM rats were recovered by acute insulin treatmen t to restore glucose levels to near normal. For MRu, the depressed response to increasing UP and volume expansion was not restored by acute correction of hyperglycemia in DMAI rats. However, antihistamine treatment or chronic insulin treatment recovered the MRu response to mechanical stimuli in DM r ats. Because of the desensitized CR2 and MRu activity, renorenal reflexes e licited by backflow of urine and increasing UP were depressed in DM rats. Conclusion. Despite a lack of structural changes, the operating system, sig naling ability, and renorenal reflex regulatory function of two renal affer ent nerve receptors, CR2 and MRu, are altered in the early diabetic state.