Double disruption of alpha(2A)- and alpha(2C)-adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype

Evidence demonstrates that sympathetic nervous system (SNS) activation causes osteopenia via beta(2)-adrenoceptor (beta(2)-AR) signaling. Here we show that female mice with chronic sympathetic hyperactivity owing to double knockout of adrenoceptors that negatively regulate norepinephrine release, alpha(2A)-AR and alpha(2C)-AR(alpha(2A)/alpha(2C)-ARKO), present an unexpected and generalized phenotype of high bone mass with decreased bone resorption and increased formation. In alpha(2A)/alpha(2C)-ARKO versus wild-type (WT) mice, micro-computed tomographic (mu CT) analysis showed increased, better connected, and more plate-shaped trabeculae in the femur and vertebra and increased cortical thickness in the vertebra, whereas biomechanical analysis showed increased tibial and femoral strength. Tibial mRNA expression of tartrate-resistant acid phosphatase (TRACP) and receptor activator of NF-kappa B (RANK), which are osteoclast-related factors, was lower in knockout (KO) mice. Plasma leptin and brain mRNA levels of cocaine amphetamine-regulated transcript (CART), which are factors that centrally affect bone turnover, and serum levels of estradiol were similar between mice strains. Tibial beta(2)-AR mRNA expression also was similar in KO and WT littermates, whereas alpha(2A)-, alpha(2B)- and alpha(2C)-AR mRNAs were detected in the tibia of WT mice and in osteoblast-like MC3T3-E1 cells. By immunohistochemistry, we detected alpha(2A)-, alpha(2B)-, alpha(2C)- and beta(2)-ARs in osteoblasts, osteoclasts, and chondrocytes of 18.5-day-old mouse fetuses and 35-day-old mice. Finally, we showed that isolated osteoclasts in culture are responsive to the selective alpha(2)-AR agonist clonidine and to the nonspecific alpha-AR antagonist phentolamine. These findings suggest that beta(2)-AR is not the single adrenoceptor involved in bone turnover regulation and show that alpha(2)-AR signaling also may mediate the SNS actions in the skeleton. (c) 2011 American Society for Bone and Mineral Research.

Exercise intensity optimization for men with high cardiorespiratory fitness

Exercise intensity is a key parameter for exercise prescription but the optimal range for individuals with high cardiorespiratory fitness is unknown. The aims of this study were (1) to determine optimal heart rate ranges for men with high cardiorespiratory fitness based on percentages of maximal oxygen consumption (%VO(2max)) and reserve oxygen consumption (%VO(2reserve)) corresponding to the ventilatory threshold and respiratory compensation point, and ( 2) to verify the effect of advancing age on the exercise intensities. Maximal cardiorespiratory testing was performed on 210 trained men. Linear regression equations were calculated using paired data points between percentage of maximal heart rate (%HR(max)) and %VO(2max) and between percentage of heart rate reserve (%HRR) and %VO(2reserve) attained at each minute during the test. Values of %VO(2max) and %VO(2reserve) at the ventilatory threshold and respiratory compensation point were used to calculate the corresponding values of %HRmax and %HRR, respectively. The ranges of exercise intensity in relation to the ventilatory threshold and respiratory compensation point were achieved at 78-93% of HR(max) and 70-93% of HRR, respectively. Although absolute heart rate decreased with advancing age, there were no age-related differences in %HR(max) and %HRR at the ventilatory thresholds. Thus, in men with high cardiorespiratory fitness, the ranges of exercise intensity based on %HR(max) and %HRR regarding ventilatory threshold were 78-93% and 70-93% respectively, and were not influenced by advancing age.