Abstract
An increase in glomerular filtration rate (GFR) in early diabetes mellitus is considered a risk factor for the development of diabetic nephropathy. Insulin deficiency may increase the activity of ATP-sensitive potassium channels (KATP), which could promote afferent arteriolar vasodilation und thus contribute to glomerular hyperfiltration in early diabetes mellitus. To further elucidate this hypothesis we performed renal clearance experiments in anesthetized rats at 2 and 6 weeks after onset of streptozotocin-induced insulin-treated diabetes mellitus and studied the acute effect of the putative KATP channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N′-cyclohexylhydrochloride (U37883A) on renal function. In control rats, application of U37883A (1.5 mg/kg i.v. bolus plus 1.5 mg/kg/hr) induced a significant reduction in heart rate, but did not affect or even slightly increased mean arterial blood pressure. Furthermore, U37883A did not significantly affect renal vascular resistance, renal blood flow or GFR, but caused an eukaliuretic diuresis and natriuresis and lowered plasma renin activity. Diabetic rats at both 2 or 6 weeks after streptozotocin exhibited essentially an identical response to U37883A; in particular, RVR and glomerular hyperfiltration remained unchanged. These results show that in both control and diabetic rats, the renal excretory function, renin secretion and pace setting in the heart were sensitiv to U37883A, implying a functional contribution of KATP channel activity. However, in both control and diabetic rats, renal vascular resistance, renal blood flow, or GFR were not altered by U37883A. These results argue against a substantial role for KATP channels in the basal control of renal hemodynamics in both nondiabetic and diabetic rats.
Footnotes
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Send reprint requests to: Volker Vallon, M.D., Department of Pharmacology, University of Tübingen, Wilhelm-Str. 56, D-72074 Tübingen, Germany. E-mail:volker.vallon{at}uni-tuebingen.de
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↵1 This work was supported by grants provided by the Deutsche Forschungsgemeinschaft (DFG Va 118/3–1, DFG Os 42/9–1) and the Federal Ministry of Education, Science, Research and Technology (BMBF 01EC9405 and 01KS9602).
- Abbreviations:
- BGL
- blood glucose level
- FF
- filtration fraction
- GFR
- glomerular filtration rate
- Hct
- arterial hematocrit
- HR
- heart rate
- [K+]
- plasma plasma potassium concentration
- MAP
- mean systemic arterial blood pressure
- [Na+]
- plasma plasma sodium concentration
- PRA
- plasma renin activity
- RBF
- renal blood flow
- RNaR
- renal sodium reabsorption
- RVR
- renal vascular resistance
- TGF
- tubuloglomerular feedback
- UV
- urinary flow rate
- UKV
- urinary potassium excretion
- UNaV
- urinary sodium excretion
- Received February 12, 1998.
- Accepted May 12, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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