American Journal of Physiology. Heart and Circulatory Physiology
G protein-coupled receptor/adenylyl cyclase (AC)/cAMP signaling is crucial for all cellular responses to physiological and pathophysiological stimuli. There are nine isoforms of membrane-bound AC, with type 5 being one of the two major isoforms in the heart. Since the role of AC in the heart in regulating cAMP and acute changes in inotropic and chronotropic state are well known, this review will address our current understanding of the distinct regulatory role of the AC5 isoform in response to chronic stress.
BACKGROUND AND AIMS: The primary purpose of the present study was to investigate the effects of 10, 25, and 40% dietary restriction (DR) on non-neoplastic diseases in rodents at 58 and 110 weeks of age, and to determine whether low-level DR (10 and 25%) can increase the survival rate and decrease variability in chronic bioassay studies.
Rapamycin has been shown to extend lifespan in numerous model organisms including mice, with the most dramatic longevity effects reported in females. However, little is known about the functional ramifications of this longevity-enhancing paradigm in mammalian tissues. We treated 24-month-old female C57BL/6J mice with rapamycin for 3†months and determined health outcomes via a variety of noninvasive measures of cardiovascular, skeletal, and metabolic health for individual mice.
In diabetes and hypertension, the induction of increased transforming growth factor-beta (TGF-beta) activity due to glucose and angiotensin II is a significant factor in the development of fibrosis and organ failure. We showed previously that glucose and angiotensin II induce the latent TGF-beta activator thrombospondin-1 (TSP1).
In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies are termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies is imperative.
Vascular endothelial dysfunction is determined by both genetic and environmental factors that cause decreased bioavailability of the vasodilator nitric oxide. This is a hallmark of atherosclerosis, hypertension, and coronary heart disease, which are major complications of metabolic disorders, including diabetes and obesity. Several therapeutic interventions, including changes in lifestyle as well as pharmacologic treatments, are useful for improving endothelial dysfunction in the face of lipotoxicity.
During 1977 and 1978, 17 obese but otherwise healthy adult Americans died suddenly of ventricular arrhythmias during or shortly after completing rapid, massive weight reduction induced by very low-calorie diets consisting largely of collagen hydrolysates for 2 to 8 months. A reexamination of the data on these victims has disclosed a significant positive correlation (r = 0.824) between their prediet body mass index and their duration of survival on the very low-calorie diets.
The relative protective effects of modifying dietary protein, fat, fiber, and energy content vs moderate food or dietary restriction (DR) on spontaneous cardiomyopathy of Charles River male Sprague-Dawley (SD) rats was evaluated at 1 and 2 years. For 2 years, SD rats were fed Purina Rodent Chow 5002 (21.4% protein, 5.7% fat, 4.1% fiber, 3.1 kcal/g) or a modified rodent chow 5002-9 (13.6% protein, 4.6% fat, 15.7% crude fiber, 2.4 kcal/g) ad libitum (AL) or by moderate DR at approximately 65% of the caloric intake of the AL group fed the 5002 diet.