Longitudinal 1H MRS of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development.

This study represents the first longitudinal, within-subject (1) H MRS investigation of the developing rat brain spanning infancy, adolescence and early adulthood. We obtained neurometabolite profiles from a voxel located in a central location of the forebrain, centered on the striatum, with smaller contributions for the cortex, thalamus and hypothalamus, on postnatal days 7, 35 and 60. Water-scaled metabolite signals were corrected for T1 effects and quantified using the automated processing software LCModel, yielding molal concentrations.

Myocardial preconditioning against ischemia-reperfusion injury is abolished in Zucker obese rats with insulin resistance.

Insulin resistance (IR) precedes the onset of Type 2 diabetes, but its impact on preconditioning against myocardial ischemia-reperfusion injury is unexplored. We examined the effects of diazoxide and ischemic preconditioning (IPC; 5-min ischemia and 5-min reperfusion) on ischemia (30 min)-reperfusion (240 min) injury in young IR Zucker obese (ZO) and lean (ZL) rats. ZO hearts developed larger infarcts than ZL hearts (infarct size: 57.

Impaired endothelin-induced vasoconstriction in coronary arteries of Zucker obese rats is associated with uncoupling of [Ca2+]i signaling.

Although insulin resistance (IR) is a major risk factor for coronary artery disease, little is known about the regulation of coronary vascular tone in IR by endothelin-1 (ET-1). We examined ET-1 and PGF(2alpha)-induced vasoconstriction in isolated small coronary arteries (SCAs; approximately 250 microM) of Zucker obese (ZO) rats and control Zucker lean (ZL) rats. ET-1 response was assessed in the absence and presence of endothelin type A (ET(A); BQ-123), type B (ET(B); BQ-788), or both receptor inhibitors.

Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production.

Insulin-resistance induces cerebrovascular dysfunction and increases the risk for stroke. We investigated whether rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, can reverse reduced cerebrovascular responsiveness in insulin-resistant rats. Dilator responses of the basilar artery (BA) were examined after 1-day or 4-wk RSV (2 mg.

Impaired insulin-induced vasodilation in small coronary arteries of Zucker obese rats is mediated by reactive oxygen species.

Insulin resistance (IR) and associated hyperinsulinemia are major risk factors for coronary artery disease. Mechanisms linking hyperinsulinemia to coronary vascular dysfunction in IR are unclear. We evaluated insulin-induced vasodilation in isolated small coronary arteries (SCA; approximately 225 microm) of Zucker obese (ZO) and control Zucker lean (ZL) rats.

Rosuvastatin treatment reverses impaired coronary artery vasodilation in fructose-fed, insulin-resistant rats.

Insulin resistance (IR) impairs vascular responses in coronary arteries, but mechanisms of dysfunction and approaches to treatment remain unclear. We examined the ability of a new 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, rosuvastatin, to reverse reduced dilator responses in rats made IR by feeding a fructose-rich diet (FF). Sprague-Dawley rats were randomized to control (normal rat diet) or FF.

Fructose-fed rats are protected against ischemia/reperfusion injury.

This study examines the relationship between insulin resistance (IR) induced by fructose feeding (FF) and susceptibility to myocardial ischemia/reperfusion injury (MI/R). Six-week-old male Sprague-Dawley rats were randomized into control (CON; n = 59) or FF (n = 58) groups. After 4 weeks, rats were further randomized into one of the following groups: placebo, ischemic preconditioning (IPC), 5-hydroxydecanoic acid (5-HD) (10 mg/kg), or 5-HD + IPC.

Arachidonic acid-induced vasodilation of rat small mesenteric arteries is lipoxygenase-dependent.

We examined the mechanism of arachidonic acid-induced vasodilation in rat small mesenteric arteries and determined the primary arachidonic acid metabolites produced by these arteries. Responses to arachidonic acid in small mesenteric arteries from Sprague-Dawley rats were investigated in vitro in the presence or absence of endothelium or after pretreatment with inhibitors of nitric oxide (NO), cyclooxygenase, cytochrome P450, lipoxygenase, or K+ channels. In addition, the metabolism of arachidonic acid was examined by incubating arteries with [3H]arachidonic acid in the presence and absence of cyclooxygenase, cytochrome P450, or lipoxygenase inhibitors.