Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled streptozotocin (STZ)-induced diabetes is attributable to diabetes-induced structural changes in the renal vasculature. Vehicle-treated control rats (CR) and rats that were injected with STZ (STZR) after pretreatment with 3-O-methylglucose (3-OMG), an agent that prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (ml·min-1·g kidney wt-1, electromagnetic flow probe), systemic arterial pressure (BP, mmHg), and renal vascular resistance (RVR, BP/RBF) in pentobarbital-anesthetized rats during a control period were 5.4 ± 0.3 (P < 0.001 vs. CR), 116 ± 3, and 21.9 ± 1.0 (P < 0.01 vs. CR) in STZR (n = 12) and 8.2 ± 0.4, 121 ± 2, and 15.3 ± 1.0 in CR (n = 11), respectively. Basal values of RBF, BP, and RVR in 3-OMG-pretreated STZR were identical to CR. The relative capacity of STZR and CR kidneys for vasodilatation in situ in response to intrarenal arterial infusions of acetylcholine (ACh) and bradykinin (BK) and systemically administered sodium nitroprusside (NP) was evaluated. The capacity of STZR to exhibit active renal vasodilatation in response to intrarenal arterial ACh and BK was significantly less than that of CR (P < 0.01). The minimum level to which RVR was suppressed after 50 μg NP/kg iv was higher in STZR than in either CR or 3-OMG-pretreated STZR (14.8 ± 1.5 vs. 9.0 ± 0.7 and 9.3 ± 1.5 mmHg·ml-1·min·g kidney wt, respectively; P < 0.05). This dose of NP exerted effective functional antagonism of renal vasoconstriction induced by exogenous norepinephrine and angiotensin II. These in vivo studies suggest that the elevated RVR in STZR might be attributable in part to structural changes in the renal vasculature that are associated with the diabetic state and limit the capacity for renal vasodilatation. However, there was no difference in pressure-flow relationships between the two groups in maximally dilated isolated kidneys perfused with Krebs buffer containing 5% albumin, and the RBF deficit in STZR kidneys was corrected by perfusion with blood from CR. Thus the decreased RBF exhibited by STZR in vivo cannot be attributed solely to renal vascular structural changes associated with diabetes. These findings suggest that undefined humoral factors or abnormal interaction of formed blood elements with vessel walls may account for elevated RVR in STZR.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - 1987|