Abstract-Exercise training attenuates arterial hypertension and increases baroreflex sensitivity in spontaneous hypertension. However, no information exists regarding the portion of the baroreflex arch in which this attenuation takes place. We tested the hypothesis that exercise training increases the afferent pathway sensitivity of baroreflex control in both normotensive and spontaneously hypertensive rats (SHR). Arterial pressure and whole-nerve activity of the aortic baroreceptor (multifiber preparation) were evaluated in 30 male rats assigned to 4 groups: sedentary and exercise-trained normotensive rats and sedentary and exercise-trained SHR. Exercise training was performed on a motor treadmill, 5 d/wk for 60 minutes, gradually progressing toward a speed of 26.8 m/min. Exercise training reduced mean arterial pressure in conscious exercise-trained SHR (183Ϯ4 versus 165Ϯ7 mm Hg). The relation between changes in aortic baroreceptor discharge and changes in systolic arterial pressure increased significantly in exercise-trained normotensive rats (2.09Ϯ0.1 versus 1.44Ϯ0.1%/mm Hg) and exercise-trained SHR (0.92Ϯ0.1 versus 0.71Ϯ0.1%/mm Hg) compared with their respective sedentary rats. Likewise, the average aortic baroreceptor gain sensitivity (calculated by logistic equation) was significantly higher in exercise-trained normotensive rats (2.25Ϯ0.19 versus 1.77Ϯ0.03%/mm Hg) and exercise-trained SHR (1.07Ϯ0.04 versus 0.82Ϯ0.05%/mm Hg) compared with their respective sedentary control rats. In conclusion, exercise training increases aortic baroreceptor gain sensitivity in normotensive and SHR, thus improving baroreceptor sensitivity, which may result in a more efficient arterial pressure regulation by the baroreflexes.
Although aberrant reactivation of embryonic gene programs is intricately linked to pathological heart disease, the transcription factors driving these gene programs remain ill-defined. Here we report that increased calcineurin/Nfat signalling and decreased miR-25 expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium. In line, mutant mice overexpressing Hand2 in otherwise healthy heart muscle cells developed a phenotype of pathological hypertrophy. Conversely, conditional gene-targeted Hand2 mice demonstrated a marked resistance to pressure-overload-induced hypertrophy, fibrosis, ventricular dysfunction and induction of a fetal gene program. Furthermore, in vivo inhibition of miR-25 by a specific antagomir evoked spontaneous cardiac dysfunction and sensitized the murine myocardium to heart failure in a Hand2-dependent manner. Our results reveal that signalling cascades integrate with microRNAs to induce the expression of the bHLH transcription factor Hand2 in the postnatal mammalian myocardium with impact on embryonic gene programs in heart failure.
Dynamic exercise training has been recommended as an antihypertensive therapy and as a way to modify the effects of many cardiovascular risk factors (Arakawa, 1993; Arroll and Beaglehole, 1992; Kelly and McClellan, 1994: see references 1–3 in the paper). However, the mechanisms underlying the blood‐pressure lowering effect of chronic exercise are still poorly understood. It has been suggested that a decrease in sympathetic tone is one of the major effects elicited by chronic exercise on the cardiovascular system. The importance of the sympathetic component is confirmed in this review, since it was found that in spontaneously hypertensive rats (SHR) a marked decrease in sympathetic activity occurred after exercise training. Moreover, our findings suggest that this effect is mediated by improving the depressed baroreceptor function, which is, in part, responsible for the attenuation of the baroreflex sensitivity observed in the sedentary SHR (Krieger et al., 1998, 1999; see references 4 and 5 in the paper).
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