Inhibition of Nitric Oxide Synthesis in Forearm Vasculature of Insulin-Dependent Diabetic Patients: Blunted Vasoconstriction in Patients with Microalbuminuria

Abstract

1. Microalbuminuria is a risk factor for cardiovascular disease in patients with insulin-dependent diabetes mellitus, and may be a marker of microvascular dysfunction including endothelial damage. The purpose of this study was to determine whether vasoconstrictor responses to NG-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis, differ between healthy subjects and insulin-dependent patients with or without microalbuminuria. 2. Twenty-eight insulin-dependent diabetic patients (14 with normal albumin excretion, 14 with microalbuminuria) were studied under euglycaemic conditions, together with 14 healthy control subjects. Forearm vascular responses to brachial artery infusions of NG-monomethyl-L-arginine, sodium nitroprusside (an endothelium-independent nitrovasodilator) and carbachol (an endothelium-dependent vasodilator) were determined by strain gauge plethysmography. 3. Basal blood flow and vasodilator responses were similar in each group. NG-Monomethyl-L-arginine reduced blood flow by 41.3 +/- 2.3% (mean +/- SEM) in healthy control subjects, 34.0 +/- 3.4% in diabetic patients without microalbuminuria and 29.2 +/- 2.0% in diabetic patients with microalbuminuria. Diabetic patients differed from healthy subjects (P = 0.005), due to a difference between control subjects and microalbuminuric diabetic patients (P < 0.001). NG-Monomethyl-L-arginine did not influence nitroprusside responses but reduced carbachol responses in control subjects and normoalbuminuric diabetic patients but not in microalbuminuric diabetic patients. 4. These results provide evidence of abnormal endothelium-derived relaxing factor/nitric oxide biosynthesis in insulin-dependent diabetic patients with microalbuminuria.

Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.

“…Differences in endothelial function between microalbuminuric and normoalbuminuric diabetic subjects have been reported (10), although these findings have not been confirmed by other investigators (23). Given the significantly attenuated vasodilatory responses to ACh after indomethacin infusion, this study demonstrates the importance of vasodilatory prostaglandins in determining regulatory tone in type 1 diabetes.…”

“…Studies that have examined responses to ACh or the muscarinic agonists in type 1 diabetes have been conflicting (7)(8)(9)(10), despite the apparent attenuated NO activity that has been observed in diabetes (9,10). There is evidence that vasodilatory prostanoids may be important in determining responses to ACh in both diabetic (4) and nondiabetic subjects (11,12), their effects being mediated through an increase in cyclic AMP.…”

Linking erectile dysfunction and coronary artery disease

“…15 Endothelial function may also be related to microalbuminuria, which appears to influence endothelium-dependent and -independent vasodilation. 40,41 Type II. Patients with type II DM have impaired vasodilation in response to both endotheliumdependent and -independent agonists.…”

Effect of Zinc Supplementation on Microalbuminuria in Patients With Type 2 Diabetes: A Double Blind, Randomized, Placebo-Controlled, Cross-Over Trial

“…Zinc is a part of these enzymes' structures and its deficiency may impair their synthesis [5]. Another hypothesis is that hyperglycemia causes endothelial cell dysfunction through a number of pathways, including increased oxidative stress [6,7] and impaired endothelium-derived relaxing factors such as nitric oxide [8,9]. In comparison with nondiabetic individuals, diabetic patients have an inferior antioxidant status [5].…”