Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients

Abstract

McNulty PH, Tulli MA, Robertson BJ, Lendel V, Harach LA, Scott S, Boehmer JP. Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients. Am J Physiol Heart Circ Physiol 293: H103-H108, 2007. First published March 16, 2007; doi:10.1152/ajpheart.00779.2006.-Patients with diabetes mellitus exhibit postprandial hyperglycemia, systemic oxidative stress, impaired endothelium-dependent, nitric oxide (NO)-mediated coronary artery dilatation, and an increased incidence of coronary events. Whether hyperglycemia causally mediates these associations is unknown. To test the hypothesis that postprandial hyperglycemia acutely impairs coronary endothelial function in humans, we compared the ability of the endothelium-dependent vasodilator acetylcholine to increase conduit coronary diameter (the macrovascular response) and coronary blood flow velocity (the microvascular response) in 12 cardiac transplant recipients without diabetes before and after blood glucose was raised from 6.7 Ϯ 1.3 mmol/l (121 Ϯ 24 mg/dl) to 17.8 Ϯ 1.5 mmol/l (321 Ϯ 27 mg/dl) for 1 h. Hyperglycemia acutely doubled circulating levels of the oxidation product malondialdehyde, indicating systemic oxidative stress, but did not affect the ability of acetylcholine to dilate conduit coronary segments or accelerate coronary blood flow. We conclude that the oxidative stress associated with a single acute episode of hyperglycemia affects neither acetylcholine-mediated coronary endothelial NO release nor the subsequent bioavailability, metabolism, or action of NO within the coronary circulation of cardiac transplant recipients. These observations imply that the relationship among hyperglycemia, oxidative stress, and coronary endothelial dysfunction is presumably mediated by mechanisms operating over longer periods of time. diabetes mellitus; coronary artery; coronary endothelial dysfunction ONE OF THE EARLIEST ABNORMALITIES identified in both animal models of diabetes mellitus (29, 34) and humans with the disease (31, 32, 37) is impairment in the ability of the coronary endothelium to effect nitric oxide (NO)-mediated arterial dilatation. Several lines of evidence suggest this may be mediated by hyperglycemia. Hyperglycemia is the hallmark of diabetes and one of its earliest features. In vitro, hyperglycemia accelerates glucose consumption by endothelial cells resulting in cytosolic accumulation of diacylglycerol, activation of protein kinase C, and inhibition of endothelial NO synthase (eNOS) (12,43). Hyperglycemia also fuels the formation of reactive oxygen species (ROS) and of advanced glycosylation end products of endovascular proteins, both of which quench NO in vitro (5, 26). Perfusing the isolated rat heart with hyperglycemic solution for 1 h accelerates venous washout of nitrotyrosine (a byproduct of the reaction of ROS with NO) and increases coronary vascular resistance (9). Hyperglycemia may also stimulate the elaboration of substances [e.g., endothelin-1 (24, 35), tumor necrosis factor-␣ (11, 30)], which indirec...

Vaccarin attenuates the human EA.hy926 endothelial cell oxidative stress injury through inhibition of Notch signaling

“…Macrovascular diseases, such as atherosclerosis, are the most frequent complications of diabetes (1). Diabetes mellitus impairs endothelial function and may be an indicator of the cardiovascular disease development (2,3). Vascular endothelium is considered to play an essential role in diabetes-associated vascular dysfunction, including atherosclerosis (4).…”

Na+/Ca2+ EXCHANGER INHIBITOR AMELIORATES IMPAIRED ENDOTHELIUM‐DEPENDENT Na+ RELAXATION INDUCED BY HIGH GLUCOSE IN RAT AORTA

“…Diabetes mellitus is a serious metabolic disorder, with both micro‐ and macrovascular complications, that results in significant morbidity and mortality 1,2 . Diabetes mellitus impairs endothelial function, which can be considered the hallmark in the development of cardiovascular diseases 3,4 . Cardiovascular diseases, including accelerated atherosclerosis and microangiopathy, are typical diabetic complications related to an early endothelial dysfunction process 1 that is generally diagnosed by reduced endothelium‐dependent vasodilation.…”

“…1,2 Diabetes mellitus impairs endothelial function, which can be considered the hallmark in the development of cardiovascular diseases. 3,4 Cardiovascular diseases, including accelerated atherosclerosis and microangiopathy, are typical diabetic complications related to an early endothelial dysfunction process 1 that is generally diagnosed by reduced endotheliumdependent vasodilation. Evidence indicates that hyperglycaemia induces endothelial dysfunction through the generation of oxidative stress, 5,6 which has been suggested to be the key player in the generation of both micro-and macrovascular complications of diabetes.…”

Nitric Oxide-Mediated Coronary Flow Regulation in Patients with Coronary Artery Disease: Recent Advances

“…In cardiac transplant recipients with diabetes mellitus, postprandial hyperglycemia acutely doubled circulating levels of the oxidation product malondialdehyde, but did not affect the ability of ACh to dilate conduit coronary artery segments or accelerate coronary blood flow, suggesting that the oxidative stress associated with an acute episode of hyperglycemia affects neither ACh-mediated coronary endothelial NO release nor subsequent bioavailability. 35 Progressive worsening of functional coronary circulatory abnormalities of NO-mediated, endotheliumdependent vasodilatation occurs with increasing severity of insulin resistance and carbohydrate intolerance. 36 The levels of homocysteine, ET-1, and circulating endothelial cell in patients with coronary lesions were increased in comparison with patients with no recognizable plaque and/or stenosis, whereas the NO level was lower in those with coronary lesions, suggesting that homocysteine appears to be a predictor for preliminary or active coronary lesion.…”