Effects of dietary restriction on the change in aortic alpha 1-adrenoceptor mediated responses during aging in Fischer 344 rats.
These studies examine 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 not 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 microM), 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% in 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Gurdal
H
H
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia.
Friedman
E
E
Johnson
M D
MD
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004032:Diet; D002149:Energy Intake / Q000502:physiology*; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D007295:Inositol Phosphates; D018340:Receptors, Adrenergic, alpha-1; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine