Akademik Veri Yönetim Sistemi
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, cilt.50, sa.2, 1995 (SCI-Expanded)
These studies example changes in alpha(1)-adrenoceptor-stimulated contraction, accumulation of inositol phosphates (IPs) and calcium influx during aging, and the effect of dietary restriction. The potency of norepinephrine (NE) at stimulating aortic contraction was highest in aortas from 1-month-old rats compared to 6- or 24-month-old rats, while the potency at stimulating IP accumulation was higher in 6- and 24-month-old rats. The fact that the NE potency for IP accumulation is riot decreased with age and is even increased a little, indicates that PI hydrolysis is not limiting for contraction. The data from 24-month-old dietary restricted rats support the same idea. Dietary restriction greatly increased the potency of NE for IP accumulation in the old animals (by 20-fold), but did not restore potency for contraction. Nifedipine (1 mu M), a calcium channel blocker, inhibited the NE-stimulated aortic contractile response by 28% in 1-month, 40% in 6-month, and 67% in 24-month-old rats. While nifedipine did not inhibit NE-stimulated IP accumulation in 1-month-old aortas, it inhibited by 30% in 6-month-old aortas and by 27% ill 24-month-old aortas. Dietary restriction (DR) did influence the inhibitory effects of nifedipine. Nifedipine inhibition of NE-stimulated contraction in 24-month-old DR rats was comparable to the inhibition in 6-month-old ad libitum (ad lib) controls and was less than in 24-month-old controls. Furthermore, nifedipine was less effective at inhibiting NE-stimulated IP accumulation in aortas from 24-month-old DR rats compared to 24-month-old controls. NE-stimulated Ca-45 influx into aortic rings decreased during aging, and DR prevented this decrease. Nifedipine inhibition of NE-stimulated Ca-45 influx was comparable between the different ages and diets. Nifedipine-insensitive Ca-45 influx was not detected iii aortas from 24-month-old rats, but was present in aortas from 1- and 6-month-old mts and in 24-month-old DR rats. These results indicate that NE-stimulated responses in the Fischer 344 rat aorta become more dependent on activation of voltage operated calcium channels and extracellular calcium as the animal ages, and that at younger ages NE stimulation activates calcium influx via routes other than voltage operated calcium channels. Dietary restriction retards the age-related decline in NE-stimulated Ca++ influx and the increased dependence on extracellular Ca++ for alpha(1)-adrenoceptor responsiveness.