title: The function of vascular smooth muscle phosphodiesterase III is preserved in healthy human aging.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Elvebak
authors.forename: John H
authors.initials: JH
authors.lastname: Eisenach
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
authors.forename: Wayne T
authors.initials: WT
authors.lastname: Nicholson
mesh_terms: D000368:Aged; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D001808:Blood Vessels / Q000187:drug effects; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism*; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006262:Health; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000008:administration & dosage / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D009599:Nitroprusside; D019323:omega-N-Methylarginine; D011464:Epoprostenol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D020105:Milrinone