Advanced glycosylation end-products and NO-dependent vasodilation in renal afferent arterioles from diabetic rats

Leon C. Moore, C. Thorup, A. Ellinger, J. Paccione, D. Casellas, F. J. Kaskel

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Systemic pressor responses to acetylcholine (ACh) are reduced in DM, an effect thought to be related to quenching of nitric oxide (NO) by advanced glycosylation end-products (AGE). We studied the effects of AGE in juxtamedullary (JM) afferent arterioles (AA) from rats with 40-50 days diabetes mellitus (DM) induced via streptozotocin. JM AA were perfused in vitro with solutions containing fresh RBCs suspended in either 6% bovine albumin or 6% AGE-albumin in euglycaemic Krebs-Ringer. Autoregulatory responses were evident in the DM vessels: AA constricted 31 ± 2% (n = 9) when perfusion pressure (PP) was raised from 60 to 140 mmHg. ACh (10 μM) caused a 43 ± 15% dilation and Ca2+-channel blockade elicited a 95 ± 14% dilation at 100 mmHg PP, indicating substantial basal vascular tone in DM AA. L-NAME (0.1 mM) constricted DM AA by 21 ± 2% (n = 9) at 100 mmHg PP, indicating significant basal NO production in DM vessels. Segments of renal resistance arteries from DM rats perfused in vitro responded to muscarinic stimulation and elevated glucose levels with significant increments in NO production, as measured with an NO-sensitive electrode. This observation shows that the renal endothelial NO system is intact in DM. While AGE in the perfusate dilated control AA, they had no effect on DM AA at all PP levels, although they blunted ACh-induced dilation. Hence, although AGE do appear to have vasoactive properties in the absence of hyperglycaemia, the results of this study are inconsistent with substantial NO quenching by AGE.

Original languageEnglish (US)
Pages (from-to)101-106
Number of pages6
JournalActa Physiologica Scandinavica
Volume168
Issue number1
DOIs
StatePublished - Mar 14 2000

Keywords

  • Acetylcholine
  • Diabetes mellitus
  • Diabetic nephropathy
  • Kidney
  • L-NAME
  • Renal autoregulation
  • Streptozotocin

ASJC Scopus subject areas

  • Physiology

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