Advanced glycosylation end-products and NO-dependent vasodilation in renal afferent arterioles from diabetic rats.
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 microM) 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.
Moore
L C
LC
Department of Physiology and Biophysics, State University of New York, Stony Brook, NY 11794-8661, USA.
Thorup
C
C
Ellinger
A
A
Paccione
J
J
Casellas
D
D
Kaskel
F J
FJ
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018678:Cholinergic Agents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006706:Homeostasis; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010477:Perfusion; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance; D014661:Vasoconstriction; D014664:Vasodilation
D018678:Cholinergic Agents; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester