Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide.
It is hypothesized that methylamine (MA) and semicarbazide-sensitive amine oxidase (SSAO) activity are involved in the cardiovascular complications in human diabetics. To test this, we 1) determined the acute vasoactive effects of MA (1-1,000 micromol/l) in uncontracted and norepinephrine (NE; 1 micromol/l)-precontracted human blood vessels used for coronary artery bypass grafts [left internal mammary artery (LIMA), radial artery (RA), and right saphenous vein (RSV)]; 2) tested whether MA effects in LIMA and RSV were dependent on SSAO activity using the SSAO inhibitor semicarbazide (1 mmol/l, 15 min); 3) determined the effects of MA metabolites formaldehyde and hydrogen peroxide in LIMA and RSV; 4) tested whether the MA response was nitric oxide, prostaglandin, or hyperpolarization dependent; 5) measured the LIMA and RSV cGMP levels after MA exposure; and 6) quantified SSAO activity in LIMA, RA, and RSV. In NE-precontracted vessels, MA stimulated a biphasic response in RA and RSV (rapid contraction followed by prolonged relaxation) and dominant relaxation in LIMA (mean +/- SE, %relaxation: 55.4 +/- 3.9, n = 30). The MA-induced relaxation in LIMA was repeatable, nontoxic, and age independent. Semicarbazide significantly blocked MA-induced relaxation (%inhibition: 82.5 +/- 4.8, n = 7) and SSAO activity (%inhibition: 98.1 +/- 1.3, n = 26) in LIMA. Formaldehyde (%relaxation: 37.3 +/- 18.6, n = 3) and H(2)O(2) (%relaxation: 55.6 +/- 9.0, n = 9) at 1 mmol/l relaxed NE-precontracted LIMA comparable with MA. MA-induced relaxation in LIMA was nitric oxide, prostaglandin, and possibly cGMP independent and blocked by hyperpolarization. We conclude that vascular SSAO activity may convert endogenous amines, like MA, to vasoactive metabolites.
Conklin
D J
DJ
Department of Medicine, University of Louisville, Louisville, KY 40202, USA. dj.conklin@louisville.edu
Cowley
H R
HR
Wiechmann
R J
RJ
Johnson
G H
GH
Trent
M B
MB
Boor
P J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000818:Animals; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D008744:Methylamines / Q000494:pharmacology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D012044:Regression Analysis; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D008744:Methylamines; D014662:Vasoconstrictor Agents; D005557:Formaldehyde; D006861:Hydrogen Peroxide; C027451:methylamine; D006631:Amine Oxidase (Copper-Containing)