Vascular wall reactivity in conductance and resistance arteries: differential effects of insulin resistance

Abstract

Insulin resistance is associated with an increased risk of cardiovascular disease that is probably related to abnormalities of vascular wall function. The JCR:LA-cp rat is a unique animal model of human vascular disease that exhibits a profound insulin resistance, vasculopathy, and cardiovascular disease, and allows study of the relationships between insulin resistance and vascular function. Conductance and resistance arteries serve different functions, thus vascular disease may affect these types of artery differently. Concentration-response curves to norepinephrine, phenylephrine, and acetylcholine were studied in conductance vessels (aortic rings) and resistance vessels (mesenteric arteries) from 12-week-old male obese and lean JCR:LA-cp rats. The aortic rings and mesenteric arteries from obese rats showed increased maximal response to phenylephrine compared with those from lean rats, whereas only the mesenteric arteries from obese rats showed increased maximal response to norepinephrine. In aortic rings, relaxation to acetylcholine was similar for both genotypes, but the mesenteric arteries of obese rats showed impaired relaxation to acetylcholine. We conclude that the sensitivity to vasoconstriction is enhanced in aortic rings and mesenteric arteries of obese male JCR:LA-cp rats, but endothelial function is impaired only in the mesenteric resistance arteries of these animals. Hence functional aberrations in the obese, insulin-resistant state are more pronounced in mesenteric resistance arteries than in a major conductance artery.

Reduced plasma volume and mesenteric vascular reactivity in obese Zucker rats

“…tractility to adrenergic stimulation in aortas (3,17,18), and striking hyperreactivity is also observed in isolated microvessels from the hindlimb (23). However, rapid pressor responses to adrenergic stimulation are mediated less by the aorta or skeletal muscle circulation but more by the mesenteric circulation, as suggested by Fig.…”

“…However, previous work has primarily evaluated vascular responses in vitro and in beds that contribute little to the systemic pressor response to injected adrenergic agents. Most studies have been performed either in the aorta (6,17) or large conduits such as the carotid (5). Conduit arteries contribute little to the regulation of vascular resistance, and thus changes in this portion of the circulation may be more relevant to vasospasm than pressor reactivity.…”

“…Exaggerated adrenergically mediated vascular reactivity has been documented in obese rat aortic rings (3,17,18) and the microcirculation of the hindlimb (23). In clinical studies, humans with higher adiposity display augmented noradrenergicmediated reductions in forearm blood flow (16).…”

Enhanced vascular contractility and diminished coronary artery flow in rats made hypertensive from diet-induced obesity

“…[10][11][12][13][14][15] However, human obesity primarily results from alterations in a combination of different genes (i.e., polygenic) that interact with environmental factors such as diet to promote aspects of the metabolic syndrome. Outbred Sprague-Dawley rats respond to a moderately high fat (MHF) diet with either an obesityprone (OP) or obesity-resistant (OR) phenotype.…”

Rimonabant-mediated changes in intestinal lipid metabolism and improved renal vascular dysfunction in the JCR:LA-cprat model of prediabetic metabolic syndrome

“…More recently, the role of the CB 1 receptor in intestinal physiology, intestinal inflammation, and conditions of obesity has become apparent (21,22). In this study, we have explored this possibility with emphasis on metabolic, lipid, and macro-and microvascular endpoints using an established animal model, the JCR:LA-cp rat.The JCR:LA-cp rat is a unique strain that has been used extensively in the study of the underlying mechanisms of the cardiovascular and renal disease associated with the metabolic syndrome (26,27,35,37,40,43,51,60), including advanced intimal (atherosclerotic) lesions, macrovascular dysfunction, myocardial ischemic lesions, and microvascular renal dysfunction (34, 49). The obese, disease-prone phenotype is due to the cp mutation that results in a stop codon in the extracellular domain of the leptin receptor (ObR) (65) and absence of all…”