Effects of advanced glycosylation end-products (age) on autoregulation in afferent arterioles (aa) from diabetic rats. † 1647

Effects of advanced glycosylation end-products (age) on autoregulation in afferent arterioles (aa) from diabetic rats. † 1647

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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 streptozotocin. 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: 10μM ACh caused a 48±6% dilation and calcium 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. Funded by Juvenile Diabetes Foundation International Grant #195079. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Pediatrics, SUNY, Stony Brook, New York, Physiology/Biophysics, SUNY, Stony Brook, New York Adam Ellinger, Jennifer Paccione, Leon C Moore & Frederick J Kaskel Authors * Adam Ellinger View author publications You can also search for this author inPubMed Google Scholar * Jennifer Paccione View author publications You can also search for this author inPubMed Google Scholar * Leon C Moore View author publications You can also search for this author inPubMed Google Scholar * Frederick J Kaskel View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ellinger, A., Paccione, J., Moore, L. _et al._ EFFECTS OF ADVANCED GLYCOSYLATION END-PRODUCTS (AGE) ON AUTOREGULATION IN AFFERENT ARTERIOLES (AA) FROM DIABETIC RATS. † 1647. _Pediatr Res_ 41 (Suppl 4), 277 (1997). https://doi.org/10.1203/00006450-199704001-01666 Download citation * Issue Date: 01 April 1997 * DOI: https://doi.org/10.1203/00006450-199704001-01666 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

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 streptozotocin. 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: 10μM ACh caused a 48±6% dilation and calcium 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. Funded by Juvenile Diabetes Foundation International Grant #195079. AUTHOR INFORMATION AUTHORS AND


AFFILIATIONS * Pediatrics, SUNY, Stony Brook, New York, Physiology/Biophysics, SUNY, Stony Brook, New York Adam Ellinger, Jennifer Paccione, Leon C Moore & Frederick J Kaskel Authors *


Adam Ellinger View author publications You can also search for this author inPubMed Google Scholar * Jennifer Paccione View author publications You can also search for this author inPubMed 


Google Scholar * Leon C Moore View author publications You can also search for this author inPubMed Google Scholar * Frederick J Kaskel View author publications You can also search for this


author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ellinger, A., Paccione, J., Moore, L. _et al._ EFFECTS OF ADVANCED


GLYCOSYLATION END-PRODUCTS (AGE) ON AUTOREGULATION IN AFFERENT ARTERIOLES (AA) FROM DIABETIC RATS. † 1647. _Pediatr Res_ 41 (Suppl 4), 277 (1997).


https://doi.org/10.1203/00006450-199704001-01666 Download citation * Issue Date: 01 April 1997 * DOI: https://doi.org/10.1203/00006450-199704001-01666 SHARE THIS ARTICLE Anyone you share the


following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer


Nature SharedIt content-sharing initiative