Age-Related Changes in Responsiveness of the Rat Aorta to Depolarizing and Receptor-Mediated Contractile Stimuli and to Calcium Antagonism

This study was undertaken to determine the relative age-dependent responsiveness of the rat aorta to depolarizing (potassium) and receptor-activating (norepinephrine) contractile stimulants, and to the calcium antagonists propyl-methylenedioxyindene (pr-MDI) and nifedipine. Pr-MDI exhibits intracellular calcium antagonistic and calcium channel blocking properties in this tissue, while nifedipine acts principally as a calcium channel blocker. Thoracic strips from young (4-6 months old) and senescent (22-23 months old) Fischer F344 rats were contracted with KCl (10-60 mmol/l) or norepinephrine (10(-9)-5 X 10(-6) mol/l). Aortae from old rats were significantly more sensitive to norepinephrine than aortae from young rats, while the reverse was observed for KCl. Pr-MDI (10(-5)-10(-4) mol/l) significantly relaxed the aortic contractions induced by norepinephrine (10(-7) mol/l, a nondepolarizing concentration producing 88% of maximum response in young and old aortae) and by KCl (50 mmol/l, a depolarizing concentration producing 96% of maximum response in young and old aortae). However, there were no age-related differences in sensitivity to the relaxant effects of pr-MDI against either stimulant. Pr-MDI was more effective in relaxing KCl-induced contractions than those induced by norepinephrine. Similar results were obtained with nifedipine (10(-10)-10(-6) mol/l). These results indicate that senescence of the rat aorta is accompanied by an enhanced responsiveness of adrenergic alpha-receptor-mediated contraction, a reduced responsiveness to depolarizing stimuli, and no change in sensitivity to calcium antagonism.