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Changes in eNOS phosphorylation contribute to increased arteriolar NO release during juvenile growth.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2012 Feb 01; Vol. 302 (3), pp. H560-6. Date of Electronic Publication: 2011 Dec 02. - Publication Year :
- 2012
-
Abstract
- Nitric oxide (NO) mediates a major portion of arteriolar endothelium-dependent dilation in adults, but indirect evidence has suggested that NO contributes minimally to these responses in the young. Isolated segments of arterioles were studied in vitro to verify this age-related increase in NO release and investigate the mechanism by which it occurs. Directly measured NO release induced by ACh or the Ca(2+) ionophore A-23187 was five- to sixfold higher in gracilis muscle arterioles from 42- to 46-day-old (juvenile) rats than in those from 25- to 28-day-old (weanling) rats. There were no differences between groups in arteriolar endothelial NO synthase (eNOS) expression or tetrahydrobiopterin levels, and arteriolar l-arginine levels were lower in juvenile vessels than in weanling vessels (104 ± 6 vs.126 ± 3 pmol/mg). In contrast, agonist-induced eNOS Thr(495) dephosphorylation and eNOS Ser(1177) phosphorylation (events required for maximal activity) were up to 30% and 65% greater, respectively, in juvenile vessels. Juvenile vessels did not show increased expression of enzymes that mediate these events [protein phosphatases 1 and 2A and PKA and PKB (Akt)] or heat shock protein 90, which facilitates Ser(1177) phosphorylation. However, agonist-induced colocalization of heat shock protein 90 with eNOS was 34-66% greater in juvenile vessels than in weanling vessels, and abolition of this difference with geldanamycin also abolished the difference in Ser(1177) phosphorylation between groups. These findings suggest that growth-related increases in arteriolar NO bioavailability may be due at least partially to changes in the regulation of eNOS phosphorylation and increased signaling activity, with no change in the abundance of eNOS signaling proteins.
- Subjects :
- Acetylcholine pharmacology
Animals
Arginine metabolism
Arterioles drug effects
Biopterins analogs & derivatives
Biopterins pharmacology
Calcimycin pharmacology
Calcium Ionophores pharmacology
Endothelium, Vascular drug effects
HSP90 Heat-Shock Proteins metabolism
Male
Muscle, Skeletal blood supply
Muscle, Skeletal growth & development
Phosphorylation physiology
Rats
Rats, Sprague-Dawley
Vasodilator Agents pharmacology
Arterioles growth & development
Arterioles metabolism
Endothelium, Vascular growth & development
Endothelium, Vascular metabolism
Nitric Oxide metabolism
Nitric Oxide Synthase Type III metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 302
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 22140037
- Full Text :
- https://doi.org/10.1152/ajpheart.00277.2011