Left ventricular remodeling with exercise in hypertension

Abstract

.-We investigated how exercise training superimposed on chronic hypertension impacted left ventricular remodeling. Cardiomyocyte hypertrophy, apoptosis, and proliferation in hearts from female spontaneously hypertensive rats (SHRs) were examined. Four-month-old SHR animals were placed into a sedentary group (SHR-SED; n ϭ 18) or a treadmill running group (SHR-TRD, 20 m/min, 1 h/day, 5 days/wk, 12 wk; n ϭ 18). Age-matched, sedentary Wistar Kyoto (WKY) rats were controls (n ϭ 18). Heart weight was greater in SHR-TRD vs. both WKY (P Ͻ 0.01) and SHR-SED (P Ͻ 0.05). Morphometricderived left ventricular anterior, posterior, and septal wall thickness were increased in SHR-SED relative to WKY and augmented in SHR-TRD. Cardiomyocyte surface area, length, and width were increased in SHR-SED relative to WKY and further increased in SHR-TRD. Calcineurin abundance was increased in SHR-SED vs. WKY (P Ͻ 0.001) and attenuated in SHR-TRD relative to SHR-SED (P Ͻ 0.05). Protein abundance and mRNA of Akt was not different among groups. The rate of apoptosis was increased in SHR-SED relative to WKY and mitigated in SHR-TRD. The abundance of Ki-67 ϩ cells across groups was not statistically different across groups. The abundance of cardiac progenitor cells (c-Kit ϩ cells) was increased in SHR-TRD relative to WKY. These data suggest that exercise training superimposed on hypertension augmented cardiomyocyte hypertrophy, despite attenuating calcineurin abundance. Exercise training also mitigated apoptosis in hypertension and showed a tendency to enhance the abundance of cardiac progenitor cells, resulting in a more favorable cardiomyocyte number in the exercise-trained hypertensive heart. hypertrophy; myocytes; apoptosis; proliferation CHRONIC HYPERTENSION INDUCES overall cardiac enlargement, which is, in part, due to cardiomyocyte hypertrophy. This is a significant health issue, since pathological cardiac enlargement increases the risk for the development of congestive heart failure (4). Increased apoptosis has also been noted in the hypertensive heart, which may be an integral substrate in overall remodeling and progression to heart failure (33).Several studies have reported that cardiac myocytes are capable of mitotic division and proliferation (13,14). While the control mechanisms for the induction of cardiomyocyte proliferation remain unclear, one theory purports the involvement of a resident population of cardiac progenitor cells (1, 30), which have been shown to increase their activity in stress-induced pathological conditions (1,28,31). In the hypertensive heart, cardiomyocyte proliferation may counteract apoptosis, thus reducing the progressive loss of cardiomyocytes.Recent studies from our laboratory, as well as others, have shown an overall phenotypical improvement for the myocardium with exercise training in hypertension (3,17,24,34,35,42). However, the precise putative mechanisms associated with the observed adaptations with exercise training remain unclear. Our present hypothesis is that exercise training in hypertension ...

Cardiac Effects of Exercise Training in Hypertension

“…Our laboratory has reported whole heart hypertrophy with echocardiography and histomorphometry with exercise training that is dispersed across several walls of the le ventricular myocardium (anterior, posterior, and septal walls). Isolated cardiomyocytes from exercise trained SHR were both longer and wider relative to sedentary controls [25]. Similar �ndings in swim-trained animals have been reported, such that swim training increased le ventricular weight and le ventricular internal diastolic diameter in the spontaneously hypertensive rats [61].…”

“…Several reports have shown that the heart contains resident cardiac stem cells that are capable of generating new cardiac tissue including cardiomyocytes [26][27][28]. We have recently shown that hypertension slightly increases cardiomyocyte proliferation and the number of c-Kit+ cells in hypertensive rodent myocardium [25]. However, hypertension-induced cell death occurs to a greater extent than cell proliferation, perhaps rendering the hypertensive myocardium with lesser number of functional cells relative to normotensive controls.…”

“…However, even though chronic exercise training reduces heart rate and blood pressure, it has been shown to increase hypertrophy at both the whole heart and cellular level in laboratory animals [25]. Our laboratory has reported whole heart hypertrophy with echocardiography and histomorphometry with exercise training that is dispersed across several walls of the le ventricular myocardium (anterior, posterior, and septal walls).…”

“…us understanding the balance between cardiomyocyte proliferation and apoptosis in pressure-induced hypertrophy is important [25]. Several reports have shown that the heart contains resident cardiac stem cells that are capable of generating new cardiac tissue including cardiomyocytes [26][27][28].…”

“…e Akt pathway has been shown to be upregulated with aerobic exercise and is linked to physiologic hypertrophy and may provide protection from apoptosis [39][40][41]. However, it is unclear whether training upregulates Akt in the hypertensive heart [25,30].…”