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Early diabetes as a model for testing the regulation of juxtaglomerular NOS I
- Source :
- American Journal of Physiology-Renal Physiology. 287:F732-F738
- Publication Year :
- 2004
- Publisher :
- American Physiological Society, 2004.
-
Abstract
- Dysregulation of kidney nitric oxide synthase (NOS) I may alter renal hemodynamics in diabetes. Four types of studies were performed in anesthetized 1- to 2-wk-streptozotocin diabetic rats. 1) Glomerular filtration rate (GFR) was measured before and during NOS I blockade. Subsequent addition of nonspecific NOS blocker tested for residual NO from other isoforms. Acute systemic NOS I blockade reduced GFR only in diabetics. Nonspecific NOS blockade had no additional effect on NOS I-blocked diabetics. 2) Renal blood flow (RBF) was monitored for evidence that tubuloglomerular feedback (TGF) resets during 1 h of continuous activation with benzolamide. NOS I blockade was added to test for the role of NOS I in TGF resetting. During 1 h of TGF activation in controls, RBF initially declined and 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. The addition of 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 single-nephron GFR (SNGFR) from the late proximal tubule was measured. In controls, NOS I blockade mainly reduced SNGFR when flow through Henle's loop was high. In diabetics, NOS I blockade reduced SNGFR independently of flow through Henle's loop. In conclusion, 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.
- Subjects :
- Male
medicine.medical_specialty
Indazoles
Physiology
Renal function
Nitric Oxide Synthase Type I
Nitric Oxide
Renal Circulation
Nitric oxide
chemistry.chemical_compound
Internal medicine
Diabetes mellitus
medicine
Animals
Diabetic Nephropathies
Enzyme Inhibitors
Rats, Wistar
Tubuloglomerular feedback
Feedback, Physiological
Kidney
omega-N-Methylarginine
biology
urogenital system
Juxtaglomerular apparatus
medicine.disease
Juxtaglomerular Apparatus
Rats
Nitric oxide synthase
medicine.anatomical_structure
Endocrinology
chemistry
biology.protein
Macula densa
Nitric Oxide Synthase
Glomerular Filtration Rate
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 287
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....7d05ca8a38946ce747ee0c825562c022