Effects of advanced glycosylation end-products (AGE) on autoregulation in afferent arterioles (AA) from diabetic rats

L. C. Moore, J. Paccione, A. Ellinger, Frederick J. Kaskel

Research output: Contribution to journalArticle

Abstract

AGE have been shown to reduce systemic pressor responses to acetylcholine (ACh) and to quench nitric oxide (NO) in vitro. We studied the effects of AGE on autoregulation and the responses to ACh and NO-synthase inhibition in juxtamedullary (JM) afferent arterioles (AA) from rats with 40-50 days diabetes mellitus (DM) induced via i.p. injection of 65 mg/kg strep to zotocin. Blood glucose was 447±20 mg/dl (n= 10). JM AA were perfused in vitro with blood solutions containing fresh RBC's (Hct∼27%) suspended in either 6% bovine albumin or 6% AGE-albumin in Krebs Ringer. The superfusate also contained AGE or albumin (1%). AGE were made by incubation of 6% albumin with 0.5 M glucose for 45 days at 37° C followed by dialysis. To control for the effects of hyperglycemia, the glucose levels were 100 mg/dl in both solutions. Under these conditions, autoregulatory responses were evident: AA constricted 38±4% (n = 8) in response to increased (60-140 mmHg) perfusion pressure (PP). The same vessels showed substantial basal tone: 10 μM ACh caused a 48±6% dilation and Ca2+-channel blockade with 10 mM MnCl2 elicited a 109±11% dilation at 100 mmHg. Significant basal NO production was evident, as 0.1 mM L-NAME constricted AA by 21±2% (n = 9) at 100 mmHg PP. AGE dilated these AA (44±12% at 100 mmHg PP, n = 8) at all PP levels; addition of ACh resulted in a modest further dilation (15±9%) to diameters similar to those seen with ACh and normal perfusate. Hence, in the absence of hyperglycemia, the vasodilatory action of AGE in DM AA is inconsistent with AGE reducing NO levels.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

Fingerprint

autoregulation
Advanced Glycosylation End Products
Arterioles
Rats
Homeostasis
acetylcholine
Acetylcholine
rats
albumins
Albumins
Perfusion
nitric oxide
Pressure
Dilatation
Nitric Oxide
hyperglycemia
Medical problems
diabetes mellitus
Hyperglycemia
Diabetes Mellitus

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Effects of advanced glycosylation end-products (AGE) on autoregulation in afferent arterioles (AA) from diabetic rats. / Moore, L. C.; Paccione, J.; Ellinger, A.; Kaskel, Frederick J.

In: FASEB Journal, Vol. 11, No. 3, 1997.

Research output: Contribution to journalArticle

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