Learn More
BACKGROUND AND PURPOSE While maintaining cardiac performance, chronic β-adrenoceptor activation eventually exacerbates the progression of cardiac remodelling and failure. We examined the adverse signalling pathways mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS) after chronic β₂-adrenoceptor(More)
Stimulation of cardiomyocyte guanosine 3',5'-cyclic monophosphate (cyclic GMP) via endothelial-derived nitric oxide (NO) is an important mechanism by which bradykinin and ACE inhibitors prevent hypertrophy. Endothelial NO dysfunction and cardiac hypertrophy are morbid features of diabetes not entirely prevented by ACE inhibitors. In(More)
We have previously demonstrated that bradykinin blocks hypertrophy of isolated cardiomyocytes: this is dependent on the release of nitric oxide from endothelial cells. In the present study, we investigated the influence of endothelial dysfunction on the antihypertrophic action of bradykinin. Angiotensin II (1 microM) induced a 34 +/- 2% increase in(More)
Until recently, most of the biological effects of nitric oxide (NO) have been attributed to its uncharged state (NO*), yet NO can also exist in the reduced state as nitroxyl (HNO or NO(-)). Putatively generated from both NO synthase (NOS)-dependent and -independent sources, HNO is rapidly emerging as a novel entity with distinct pharmacology and therapeutic(More)
1. Bradykinin inhibits hypertrophy of rat ventricular myocytes, but only in the presence of endothelial cells. 2. The influence of hyperglycaemia on the ability of bradykinin to prevent hypertrophy was investigated in adult rat ventricular myocytes cocultured with bovine aortic endothelial cells (BAEC). 3. In myocytes cocultured with normal BAEC,(More)
The formation of advanced glycation end products (AGEs) on extracellular matrix components leads to accelerated increases in collagen cross linking that contributes to myocardial stiffness in diabetes. This study determined the effect of the crosslink breaker, ALT-711 on diabetes-induced cardiac disease. Streptozotocin diabetes was induced in Sprague-Dawley(More)
Cardiovascular disease is the primary cause of morbidity and mortality among the diabetic population. Both experimental and clinical evidence suggest that diabetic subjects are predisposed to a distinct cardiomyopathy, independent of concomitant macro- and microvascular disorders. 'Diabetic cardiomyopathy' is characterized by early impairments in diastolic(More)
B-type natriuretic peptide (BNP), initially identified in brain tissues, is now recognized as a key cardiac hormone. Numerous studies over the last decade have demonstrated that both exogenous and endogenous BNP prevent left ventricular (LV) hypertrophy in experimental settings, largely via activation of particulate guanylyl cyclase (pGC)-coupled receptors.(More)
OBJECTIVE Compelling epidemiological and clinical evidence has identified a specific cardiomyopathy in diabetes, characterized by early diastolic dysfunction and adverse structural remodeling. Activation of the insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) promotes physiological cardiac growth and enhances contractile function. The aim of the(More)