Richard H. Kennedy

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Interleukin (IL)-6 decreases cardiac contractility via a nitric oxide (NO)-dependent pathway. However, mechanisms underlying IL-6-induced NO production remain unclear. JAK2/STAT3 and ERK1/2 are two well known signaling pathways activated by IL-6 in non-cardiac cells. However, these IL-6-activated pathways have not been identified in adult cardiac myocytes.(More)
A recent report indicated that hyperhomocysteinemia (Hhe), in addition to its atherothrombotic effects, exacerbates the adverse cardiac remodeling seen in response to hypertension, a powerful stimulus for pathological ventricular hypertrophy. The present study was undertaken to determine whether Hhe has a direct effect on ventricular remodeling and function(More)
Ceramide, a sphingolipid metabolite produced by activation of sphingomyelinase, has been previously shown to reduce L-type Ca2+ channel current (ICa,L) in adult rat ventricular myocytes; however, its effect on contractile function is unknown. In this study, we investigated the effects of ceramide on excitation-contraction coupling in adult ventricular(More)
The proliferation of pancreatic extracellular matrix, which characterizes chronic pancreatitis, has been analysed using immunohistochemistry. The relationship of matrix components to intraductal precipitates and the presence of serum proteins in precipitates were also studied to investigate the suggestion that ductal permeability increases in chronic(More)
Tumor necrosis factor (TNF)-alpha has been shown to induce apoptosis in a variety of cell types including cardiac myocytes. Sphingosine/ceramide and nitric oxide have been associated with apoptosis induced by TNF-alpha; however, signaling mechanisms of TNF-alpha-induced apoptosis in cardiac myocytes are not well defined. This study examined whether(More)
BACKGROUND Recent studies demonstrate that hyperhomocysteinemia is a risk factor for heart failure. Oxidant stress is a major mediator of the pathogenic effects of hyperhomocysteinemia. METHODS We utilized a rat model of diet-induced hyperhomocysteinemia to examine whether treatment with an anti-oxidant vitamin (C&E) combination will prevent(More)
BACKGROUND Postulated mechanisms of hyperhomocysteinemia (Hhe) overlap with proposed mechanisms of adverse cardiac remodeling such as altered collagen metabolism and oxidant stress. Hence we examined the hypothesis that Hhe would promote myocardial fibrosis and systolic dysfunction. METHODS Three-month-old spontaneously hypertensive rats (SHRs) were(More)
Previous studies have shown that chronic hyperhomocysteinemia is associated with an adverse cardiac remodeling and heart failure. This study, which utilized coronary-perfused hearts and superfused papillary muscle, was designed to determine whether homocysteine acts acutely to alter cardiac contractile function. Left ventricular developed pressure was used(More)
Hyperhomocysteinemia (Hhe), linked to cardiovascular disease by epidemiological studies, may be an important factor in adverse cardiac remodeling in hypertension. Specifically, convergence of myocardial and vascular alterations promoted by Hhe and hypertension may exacerbate cardiac remodeling and myocardial dysfunction. We studied male spontaneously(More)
1. In general, premenopausal women are known to have lower blood pressure than men and animal models have shown a similar sexual dimorphism. However, many studies in animals have been performed using anaesthetized or restrained models. Current experiments were conducted to investigate the relationships among resting heart rate, blood pressure and gender in(More)