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ATTENUATED GLOMERULAR CGMP PRODUCTION AND RENAL VASODILATION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
Author(s): WANG YX, BROOKS DP, EDWARDS RM
Source: AMERICAN JOURNAL OF PHYSIOLOGY    Volume: 264    Issue: 5    Pages: R952-R956    Part: Part 2    Published: MAY 1993  
Times Cited: 33     References: 25     
Abstract: Because diabetes is associated with impaired vascular endothelium, we have investigated endothelium-dependent cGMP stimulation in isolated glomeruli and renal vasodilation in normal and diabetes mellitus (DM) rats. Rats treated with streptozotocin (60 mg/kg iv) developed high blood glucose, polyuria, enlarged kidneys, and slow weight gain compared with control animals. Chronic treatment with insulin reversed these changes. In isolated glomeruli, the endothelium-dependent vasodilator, acetylcholine (ACh), stimulated cGMP accumulation concentration dependently; however, the response was significantly attenuated in glomeruli from DM rats when compared with normal rats or DM rats treated with insulin. Sodium nitroprusside-induced cGMP accumulation was also slightly but significantly reduced in glomeruli from DM rats, however, the response to atriopeptin III was unaltered. In rats, intravenous infusion of ACh (1 and 10 mug.kg-1.min-1) moderately decreased blood pressure and increased renal blood flow without a significant change in glomerular filtration rate. The renal vasodilatory response to ACh was significantly diminished in DM rats, but not in DM rats treated with insulin. Acute treatment with insulin did not restore the ACh response, although the blood glucose level was normalized. We conclude that there is a reduced renal vasodilatory response observed in DM, and this is due to an impairment of the renal vascular endothelium to produce endothelium-dependent relaxation factor (nitric oxide) and/or a defective soluble guanylate cyclase.
Document Type: Article
Language: English
Addresses:
1. SMITHKLINE BEECHAM PHARMACEUT, DEPT RENAL PHARMACOL, KING OF PRUSSIA, PA 19406 USA
Publisher: AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
Subject Category: Physiology
IDS Number: LD347
ISSN: 0002-9513
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