Effects of maturation on cyclic GMP-dependent vasodilation in ovine basilar and carotid arteries.
The present experiments examine the effects of maturation on cyclic GMP (cGMP)-mediated vasodilation in 688 segments of common carotid (COM) and basilar (BAS) arteries taken from newborn (3- to 7-d-old) and nonpregnant adult sheep. The main finding is that maximum efficacy for relaxation decreased with maturation in both artery types for the nitric oxide releasing vasodilators S-nitroso-N-acetyl-penicillamine and nitroglycerin. These decreases could not be explained by changes in the -log ED50 concentrations for either vasodilator. Determination of the time course of cGMP responses to S-nitroso-N-acetyl-penicillamine or nitroglycerin at 10 microM revealed that the peak cGMP responses to these agents (range: 5.3 +/- 0.8 to 8.3 +/- 1.6 pmol/mg of protein) also did not vary significantly with age. However, cGMP attained peak values more rapidly in adult (COM: 50 s; BAS 30 s) than in newborn (COM: 60-80 s: BAS, 40-60 s) segments and returned to baseline more slowly in newborn than in adult segments, suggesting that maturation accelerates cGMP turnover. Correspondingly, baseline levels of cGMP were higher in newborn (COM: 1.0 +/- 0.1; BAS: 3.3 +/- 0.5 pmol/mg of protein) than in adult (COM: 0.3 +/- 0.1; BAS: 1.7 +/- 0.2 pmol/mg of protein) segments. Despite these differences in cGMP time course, rates of relaxation in response to S-nitroso-N-acetyl-penicillamine and nitroglycerin did not vary significantly with age, indicating that the temporal relation between cGMP and relaxation is different in newborn and adult arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Pearce
W J
WJ
Department of Physiology, Loma Linda University School of Medicine, California 92350.
Hull
A D
AD
Long
D M
DM
White
C R
CR
D000818:Animals; D000831:Animals, Newborn; D001488:Basilar Artery / Q000254:growth & development*; D001711:Biotransformation; D017536:Carotid Artery, Common / Q000254:growth & development*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005996:Nitroglycerin / Q000493:pharmacokinetics; D010396:Penicillamine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D026423:S-Nitroso-N-Acetylpenicillamine; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000493:pharmacokinetics
D014665:Vasodilator Agents; D026423:S-Nitroso-N-Acetylpenicillamine; D000242:Cyclic AMP; D005996:Nitroglycerin; D010396:Penicillamine; D006152:Cyclic GMP