title: Decreased contractile responses to isoproterenol in isolated cardiac myocytes from aging guinea-pigs.
abstract: We have characterized the age-related changes of contractility and beta-adrenoceptor function in isolated cardiac myocytes from guinea-pigs. We used either adult animals from 2 to 14 weeks of age, where body weight increases linearly with age, or senescent ones aged between 53-65 weeks. There was some indication of a decrease in contractility in maximum Ca2+ with age, with significant differences between a young (< or = 4 weeks, weight < 400 g) and aged (> or = 8 weeks, weight > 600 g) group in contraction amplitude expressed as percentage shortening (but not when expressed as micron change in length) or contraction and relaxation velocities. This decline was continued into senescence, and ANOVA showed a significant difference between the three groups for contraction amplitude (percentage shortening, 12.2 +/- 0.9%, young, n = 31; 9.5 +/- 0.6%, n = 28 aged; 6.7 +/- 0.8%, n = 6, senescent; P = 0.005), and contraction or relaxation velocities (P < 0.001). There was a more pronounced decline in maximum response to isoproterenol with age. ANOVA for the maximum isoproterenol response for the three divisions showed significant differences for percentage shortening (11.8 +/- 0.7%, n = 30, young; 7.9 +/- 0.5%, n-28, aged and 5.5 +/- 1.1%, n = 6, senescent; P < 0.001), velocities of contraction (P < 0.001) and relaxation (P < 0.001), and normalized velocities of contraction (P < 0.001) and relaxation (P < 0.01) at maximum isoproterenol, as well as in ISO EC50 (P < 0.001) and isoproterenol/Ca2+ ratio (P < 0.02). A general decrease in contractility of the myocyte occurs as the animal ages, with maximum contraction amplitude being reduced and velocity of contraction and relaxation slowed. The effect was more pronounced for beta-adrenoceptor stimulation than for high Ca2+, suggesting a specific lesion in the adenylate cyclase related pathway. Much of the change occurred between the young adult (< or = 4 weeks) and the aged adult (> or = 8 weeks), although the trend was continued in senescent animals (> 52 weeks).
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D002118:Calcium