JUXTAMEDULLARY MICROVASCULAR DYSFUNCTION DURING THE HYPERFILTRATION STAGE OF DIABETES-MELLITUS

This study was designed to identify and localize defects in renal micr ovascular function during the hyperfiltration stage of diabetes mellit us. Male Sprague-Dawley rats were injected intravenously with 65 mg/kg streptozotocin (IDDM rats) or vehicle (sham rats). IDDM rats received insulin (3 U.kg(-1).day(-1)) via an osmotic minipump; sham rats recei ved diluent. During the ensuing 2-wk period, blood glucose levels aver aged 89 +/- 2 mg/dl in 33 sham rats and 290 +/- 13 mg/dl in 37 IDDM ra ts. At the end of this period, inulin clearance was elevated in eight IDDM rats (1.43 +/- 0.17 ml.min(-1).g kidney wt(-1)) compared with six sham rats (0.78 +/- 0.05 ml.min(-1).g kidney wt(-1)). The remaining a nimals served as tissue donors for study of the renal microvasculature using the in vitro blood-perfusedjuxtamedullary nephron technique. Ki dneys from sham and IDDM rats were perfused with homologous blood at a renal arterial pressure of 110 mmHg. Juxtamedullary single-nephron gl omerular filtration rate was higher in IDDM rats (41.5 +/- 5.4 nl/min) than in sham rats (25.4 +/- 2.4 nl/min). Afferent arteriolar inside d iameter was greater in IDDM rats (34 +/- 2 mu m) than in sham rats (22 +/- 1 mu m); however, efferent arteriolar diameter did not differ bet ween groups. The afferent arteriolar vasoconstrictor response to norep inephrine (NE) was attenuated in IDDM rats, relative to sham rats, ove r a wide range of NE concentrations. In contrast, NE evoked similar de grees of efferent vasoconstriction in IDDM and sham rats. Sodium nitro prusside (SNP; 100 mu M) caused a greater afferent vasodilation in sha m than in IDDM rats, while the efferent response to SNP was comparable in both groups. These observations indicate that afferent, but not ef ferent, arterioles are nearly maximally dilated and exhibit diminished NE responsiveness during the hyperfiltration stage of diabetes. These selective changes in preglomerular function could underlie the hyperf iltration characteristic of early diabetes mellitus.