Open AccessThe Function of Vascular Smooth Muscle Phosphodiesterase III is Preserved in Healthy Human Aging
Author(s) -
Elvebak Rachel L.,
Eisenach John H.,
Joyner Michael J.,
Nicholson Wayne T.
Publication year - 2010
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2010.00232.x
Subject(s) - milrinone , sodium nitroprusside , vasodilation , medicine , endocrinology , cyclic guanosine monophosphate , phosphodiesterase , nitric oxide , vascular smooth muscle , phosphodiesterase 3 , cgmp specific phosphodiesterase type 5 , prostacyclin , chemistry , hemodynamics , sildenafil , enzyme , biochemistry , smooth muscle
Phosphodiesterase (PDE) III is an enzyme in vascular smooth muscle that metabolizes cyclic adenosine monophosphate (cAMP). Milrinone inhibits PDE III, increasing the availability of cAMP. Cyclic guanosine monophosphate (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 NG‐monomethyl‐ l ‐arginine acetate ( l ‐NMMA) to remove the confounding inhibitory effects of cGMP on PDE III. Incremental doses of PGI 2 and sodium nitroprusside (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. Clin Trans Sci 2010; Volume 3: 239–242.