Document Detail

The function of vascular smooth muscle phosphodiesterase III is preserved in healthy human aging.
MedLine Citation:
PMID:  21499513     Owner:  NLM     Status:  Publisher    
Phosphodiesterase III (PDE) is an enzyme in vascular smooth muscle that metabolizes cyclic AMP (cAMP). Milrinone inhibits PDE III, increasing the availability of cAMP. Cyclic GMP (cGMP), which is regulated by nitric oxide (NO), also inhibits PDE III. The endothelial NO component of prostacyclin (PGI(2))-mediated vasodilation is reduced in aging This study investigated if PGI(2)-mediated vasodilation during concomitant inhibition of endothelial NO and smooth muscle PDE III is affected by healthy aging. PDE III was inhibited with milrinone in 10 older subjects and 10 young matched controls while simultaneously infusing N(G)-Monomethyl-L-arginine acetate (L-NMMA) to remove the confounding inhibitory effects of cGMP on PDE III. Incremental doses of PGI(2) and SNP were administered to the brachial artery during separate trials. L-NMMA decreased baseline blood flow similarly, and the addition of milrinone increased baseline blood flow similarly in both groups. The forearm blood flow responses to PGI(2) were similar between groups (younger: 7.62 ± 0.72; older: 6.88 ± 0.81 ml·dl(-1) FAV·min(-1) at the highest dose of PGI(2)). SNP responses were also similar. This study suggests that the vasodilator pathway associated with PDE III function, the bioavailability of cAMP, and the interaction with cGMP may be preserved in healthy aging.
Rachel L Elvebak; John H Eisenach; Michael J Joyner; Wayne T Nicholson
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Publication Detail:
Journal Detail:
Title:  Clinical and translational science     Volume:  3     ISSN:  1752-8062     ISO Abbreviation:  -     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2011-4-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101474067     Medline TA:  Clin Transl Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  239-242     Citation Subset:  -    
Department of Anesthesia Research, Mayo Clinic, Rochester, MN 55905.
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Grant Support
R01 HL046493-08//NHLBI NIH HHS; T32 GM008685-06//NIGMS NIH HHS

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