Effects of diabetes and uremia on mesenteric vascular reactivity

Abstract

Diabetes and uremia are comorbid conditions that have significant effects on cardiovascular physiology. These studies were designed to examine the effects of diabetes and uremia on vascular reactivity. Sprague-Dawley rats were divided into control (C), diabetic (D), uremic (U), and diabetic/uremic (D + U) groups. Diabetes (D, D + U groups) was induced with an injection of streptozotocin. Uremic (U, D + U groups) was produced by seven-eighths nephrectomy. Serum glucose, blood urea nitrogen, creatinine, creatinine clearance, and protein excretion were measured at baseline and before microvascular studies at 4 or 8 weeks after injection. Vascular reactivity was studied in isolated, pressurized, and superfused segments of mesenteric arterioles (300 microns). Changes in internal vessel diameter were measured in response to phenylephrine (10(-8) to 10(-4) mol/L), acetylcholine (10(-9) to 10(-5) mol/L), and nitroprusside (10(-9) to 10(-2) mol/L). Results at 4 and 8 weeks were similar in all groups. Vasoconstrictor responses to phenylephrine and endothelium-independent vasodilator responses to nitroprusside were not altered in any experimental group. Endothelium-dependent vasodilator responses to acetylcholine were significantly depressed in both diabetic groups (D and D + U, p < 0.01 versus control), and there were no differences between the two diabetic groups. Streptozotocin-induced diabetes results in impairment of endothelial-dependent (nitric oxide mediated) vasodilator responses in mesenteric resistance vessels, which are unaffected by coexisting uremia. Uremia has little effect on mesenteric vascular reactivity in this model.