Vasoactive effects of methylamine in isolated human blood vessels

Role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide

D. J. Conklin, H. R. Cowley, R. J. Wiechmann, G. H. Johnson, M. B. Trent, P. J. Boor

Research output: Contribution to journalArticle

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Abstract

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 μmol/1) in uncontracted and norepinephrine (NE; 1 μmol/1)-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 2O2 (%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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number2 55-2
StatePublished - Feb 2004

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Amine Oxidase (Copper-Containing)
Mammary Arteries
Hydrogen Peroxide
Formaldehyde
Blood Vessels
Saphenous Vein
Radial Artery
Prostaglandins
methylamine
Nitric Oxide
Coronary Artery Bypass
Amines
Norepinephrine

Keywords

  • Amine metabolism
  • Coronary artery bypass grafts
  • Diabetes
  • HO

ASJC Scopus subject areas

  • Physiology

Cite this

Vasoactive effects of methylamine in isolated human blood vessels : Role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide. / Conklin, D. J.; Cowley, H. R.; Wiechmann, R. J.; Johnson, G. H.; Trent, M. B.; Boor, P. J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 286, No. 2 55-2, 02.2004.

Research output: Contribution to journalArticle

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abstract = "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 μmol/1) in uncontracted and norepinephrine (NE; 1 μmol/1)-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 2O2 ({\%}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.",
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AU - Cowley, H. R.

AU - Wiechmann, R. J.

AU - Johnson, G. H.

AU - Trent, M. B.

AU - Boor, P. J.

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