Variations in beta(1)-adrenoceptor function due to age or sex were examined in the mouse model of Duchenne muscular dystrophy. Positive chronotropic and inotropic responses to (-)-isoprenaline and antagonist effects of CGP20712A were determined in isolated right and left atria from young (12 week) and old (12 month) male and old (12 month) female mdx mice and their age- and sex-matched C57BL/10ScSn (C57) mice. There was no difference in efficacy to (-)-isoprenaline when expressed as an increase in the rate of contraction or force of contraction as a percentage of Ca(2+)-induced increase respectively in right or left atria from age- and sex-matched mdx and C57. Old mdx males showed a decreased sensitivity to (-)-isoprenaline (P<0.05) and a reduced affinity to CGP 20712A (P<0.05) in both right and left atria compared with old C57 males. These same changes were also observed in left atria between old and young mdx males. A reduced efficacy to (-)-isoprenaline was also evident when young and old mdx males were compared. In contrast, in old females, mdx showed an increased affinity to CGP20712A in left and right atria (P<0.05), and an enhanced sensitivity to (-)-isoprenaline in right atria. Finally, in left atria, the maximum Ca(2+)-induced increase in force of contraction was lower in all mdx compared to their age- and sex-matched C57 (P<0.05). In conclusion, age- and sex-associated changes in beta(1)-adrenoceptor function and responses to calcium were demonstrated in cardiac muscle from mdx mice, with a marked deterioration in beta(1)-adrenoceptor function occurring with aging in male mdx being particularly evident.
Copyright 2000 Academic Press.