We conclude that hypercholesterolemia but not hypertriglyceridemia leads to increased formation of superoxide and peroxynitrite, and thereby results in cardiac dysfunction in hearts of human apoB100 transgenic mice.

We have previously shown that capsaicin-sensitive sensory nerves contribute to the regulation of normal cardiac function and to the development of cardiac adaptation to ischemic stress; however, the underlying molecular mechanisms remain unknown. Therefore, here we assessed cardiac functional alterations and relative gene expression changes by DNA microarray analysis of 6400 genes in rat hearts 7 days after the end of systemic capsaicin treatment protocol leading to selective sensory chemodenervation. Capsaicin pretreatment resulted in a cardiac dysfunction characterized by elevation of left ventricular end-diastolic pressure and led to altered expression of 80 genes of known function or homology to known sequences. Forty-seven genes exhibited significant up-regulation and 33 genes were down-regulated (changes ranged from -3.9 to +4.8-fold). The expression changes of 10 selected genes were verified, and an additional 11 genes were examined by real-time quantitative PCR. This is the first demonstration that gene expression changes in the heart due to capsaicin pretreatment included vanilloid receptor-1 (capsaicin receptor), transient receptor potential protein, GABA receptor rho-3 subunit, 5-hydroxytryptamine 3 receptor B, neurokinin receptor 2, endothelial nitric oxide synthase, matrix metalloproteinase-13, cytochrome P450, farnesyl-transferase, ApoB, and leptin. None of the genes have been previously shown to be involved in the mechanism of the cardiac functional effects of sensory chemodenervation by capsaicin. We conclude that capsaicin-sensitive sensory nerves play a significant role in the regulation of a variety of neuronal and non-neuronal genes in the heart and possibly in other tissues as well.

This is the first demonstration in the rat myocardium that 3-NP induces pharmacological preconditioning, thereby limiting infarct size, and that this effect is associated with increased NO bioavailability and reduced peroxynitrite formation due to inhibition of superoxide formation by XO and NADH oxidase.

Cardiac expression of cytoprotective gene heme oxygenase-1 (HO-1) is modulated by ischaemia and reperfusion (I/R). We therefore hypothesized that pretreatment with hemin, an inductor of HO-1, would precondition the heart against post-ischaemic dysfunction and ventricular fibrillation (VF). Male Wistar rats were given either hemin or HO enzyme inhibitor zinc protoporphyrin IX (ZnPP IX). Isolated hearts were subjected to 30 min global ischaemia followed by 120 min of reperfusion or were aerobically perfused in a time-matched non-ischaemic protocol. Control animals received no pretreatment. Compared to non-perfused controls, pretreatment with hemin increased HO-1 mRNA 13-fold (p<0.001) and HO-1 protein 3.5-fold (p

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