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1 Department of Medicine, Division of Nephrology-Hypertension University of California, San Diego, CA, USA; Medical Research, VA San Diego Health Care System, San Diego, CA, USA
2 Department of Medicine, Division of Nephrology-Hypertension University of California, San Diego, CA, USA
* To whom correspondence should be addressed. E-mail: sthomson{at}ucsd.edu.
Dysregulation of kidney NOS-I may alter renal hemodynamics in diabetes. Four types of studies were performed in anesthetized 1-2 week streptozotocin diabetic rats: 1) GFR was measured before and during NOS-I blockade. Subsequent addition of non-specific NOS blocker tested for residual NO from other isoforms. Acute systemic NOS-I blockade reduced GFR only in diabetics. Non-specific NOS blockade had no additional effect in NOS-I blocked diabetics. 2) RBF was monitored for evidence that tubuloglomerualr feedback (TGF) resets during one hour of continuous activation with benzolamide. NOS-I blockade was added to test for the role of NOS-I in TGF resetting. During one hour of TGF activation in controls, RBF initially declined then returned to baseline. In diabetic and NOS-I blocked rats, RBF declined and remained low. 3) The ability of NOS-I blockade to increase the homeostatic efficiency of TGF in diabetes was tested by micropuncture in free flowing nephrons. Adding NOS-I blocker to the tubular fluid increased TGF efficiency in control and diabetic rats. 4) The influence of distal salt delivery on local NOS-I activity was tested by micropuncture. Henle's loop was perfused at varying rates with NOS-I blocker while measuring single nephron GFR (SNGFR) from the late proximal tubule. In controls, NOS I blockade mainly reduced SNGFR when flow through Henle's loop was high. In diabetics, NOS I blockade reduced SNGFR independent of flow through Henle's loop. Conclusions- Normally, salt delivered to the macula densa (MD) exerts immediate control over MD NOS-I activity. In diabetes there is ongoing overactivity of NOS-I that is not regulated by MD salt.
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