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Mechanisms for Renal Blood Flow Control Early in Diabetes as Revealed by Chronic Flow Measurement and Transfer Function Analysis

Tracy D. Bell^*, Gerald F. DiBona, Ying Wang and Michael W. Brands^*,

^* Department of Physiology; Vascular Biology Center, Medical College of Georgia; Department of Mathematics and Computer Science, Augusta State University, Augusta, Georgia; and Departments of Internal Medicine and Physiology & Biophysics, University of Iowa, Iowa City, Iowa

Address correspondence to: Dr. Michael W. Brands, Department of Physiology, CA-3098, Medical College of Georgia, Augusta, GA 30912-3000. Phone: 706-721-9785; Fax: 706-721-7299; mbrands{at}mcg.edu

Received for publication March 9, 2006. Accepted for publication May 16, 2006.

The purpose of this study was to establish the roles of the myogenic response and the TGF mechanism in renal blood flow (RBF) control at the very earliest stages of diabetes. Mean arterial pressure (MAP) and RBF were measured continuously, 18 h/d, in uninephrectomized control and diabetic rats, and transfer function analysis was used to determine the dynamic autoregulatory efficiency of the renal vasculature. During the control period, MAP averaged 91 ± 0.5 and 89 ± 0.4 mmHg, and RBF averaged 8.0 ± 0.1 and 7.8 ± 0.1 ml/min in the control and diabetic groups, respectively. Induction of diabetes with streptozotocin caused a marked and progressive increase in RBF in the diabetic rats, averaging 10 ± 6% above control on day 1 of diabetes and 22 ± 3 and 34 ± 1% above control by the end of diabetes weeks 1 and 2. MAP increased approximately 9 mmHg during the 2 wk in the diabetic rats, and renal vascular resistance decreased. Transfer function analysis revealed significant increases in gain to positive values over the frequency ranges of both the TGF and myogenic mechanisms, beginning on day 1 of diabetes and continuing through day 14. These very rapid increases in RBF and transfer function gain suggest that autoregulation is impaired at the very onset of hyperglycemia in streptozotocin-induced type 1 diabetes and may play an important role in the increase in RBF and GFR in diabetes. Together with previous reports of decreases in chronically measured cardiac output and hindquarter blood flow, this suggests that there may be differential effects of diabetes on RBF versus nonrenal BF control.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673