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Abstract-The long-term effects of exercise on cardiac function and myocyte remodeling in hypertension/progression of heart failure are poorly understood. We investigated whether exercise can attenuate pathological remodeling under hypertensive conditions. Fifteen female Spontaneously Hypertensive Heart Failure rats and 10 control rats were housed with running wheels beginning at 6 months of age. At 22 months of age, heart function of the trained rats was compared with heart function of age-matched sedentary hypertensive and control rats. Heart function was measured using echocardiography and left ventricular catheterization. Cardiac myocytes were isolated to measure cellular dimensions. Fetal gene expression was determined using Western blots. Exercise did not significantly impact myocyte remodeling or ventricular function in control animals. Sedentary hypertensive rats had significant chamber dilatation and cardiac hypertrophy. In exercised hypertensive rats, however, exercise time was excessive and resulted in a 21% increase in left ventricular diastolic dimension (PϽ0.001), a 24% increase in heart to body weight ratio (PϽ0.05), a 27% increase in left ventricular myocyte volume (PϽ0.01), a 13% reduction in ejection fraction (PϽ0.001), and a 22% reduction in fractional shortening (PϽ0.01) compared with sedentary hypertensive rats. Exercise resulted in greater fibrosis and did not prevent activation of the fetal gene program in hypertensive rats. We conclude that excessive exercise, in the untreated hypertensive state can have deleterious effects on cardiac remodeling and may actually accelerate the progression to heart failure. Key Words: hypertension Ⅲ heart failure Ⅲ exercise Ⅲ hypertrophy Ⅲ myocytes Ⅲ voluntary wheel running Ⅲ SHHF R esearch has shown a predictable remodeling of cardiac myocyte shape underlying progression to heart failure (HF). 1 Initially, under hypertensive conditions, there is a marked increase in myocyte cross-sectional area (CSA) whereas cell length remains normal. Between the ages of 6 and 12 months in female spontaneously hypertensive heart failure (SHHF) rats, after a period of compensated hypertrophy, myocyte length begins to increase without further increase in CSA. This excessive addition of sarcomeres in series continues until the development of overt signs of HF at 24 months. 1 In the healthy heart, aerobic exercise training has been shown to increase myocardial mass, left ventricle (LV) chamber dimensions, and stroke volume. 2,3 In LV dysfunction and in HF patients, exercise has been shown to improve exercise tolerance and symptoms. This benefit has traditionally been attributed to peripheral adaptations. More recent studies, however, indicate that beneficial changes may be occurring centrally as well. As in the healthy heart, these adaptations include increased LV wall thickness and LV function 4,5 and enhanced myocardial ␤-adrenergic responsiveness. 6 Recent studies by Iemitsu et al 7 and Emter et al 8 showed that regular exercise training results in reversal of the fetal ge...

Major depressive disorder (MDD) is a devastating disease affecting over 300 million people worldwide, and costing an estimated 380 billion Euros in lost productivity and health care in the European Union alone. Although a wealth of research has been directed toward understanding and treating MDD, still no therapy has proved to be consistently and reliably effective in interrupting the symptoms of this disease. Recent clinical and preclinical studies, using genetic screening and transgenic rodents, respectively, suggest a major role of the CRF1 gene, and the central expression of CRF1 receptor protein in determining an individual’s risk of developing MDD. This gene is widely expressed in brain tissue, and regulates an organism’s immediate and long-term responses to social and environmental stressors, which are primary contributors to MDD. This review presents the current state of knowledge on CRF physiology, and how it may influence the occurrence of symptoms associated with MDD. Additionally, this review presents findings from multiple laboratories that were presented as part of a symposium on this topic at the annual 2014 meeting of the International Behavioral Neuroscience Society (IBNS). The ideas and data presented in this review demonstrate the great progress that has been made over the past few decades in our understanding of MDD, and provide a pathway forward toward developing novel treatments and detection methods for this disorder.