title: Impact of type 2 diabetes on nitric oxide and adrenergic modulation of myocardial perfusion.
abstract: Type 2 diabetic patients are characterized by a reduced adenosine-induced hyperemic myocardial perfusion, which may contribute to their increased cardiovascular morbidity. We hypothesized that the reduced hyperemia can be explained by functional changes in endothelial or autonomic nervous regulation. In 12 type 2 diabetic patients without signs of ischemic heart disease and 14 age-matched control subjects, myocardial perfusion was measured at rest, during adenosine, and during adenosine and alpha-receptor blockade (phentolamine) using positron emission tomography on two separate days: 1) with, and 2) without nitric oxide (NO) inhibition with N(G)-nitro-L-arginine methyl ester. Myocardial perfusion during adenosine was lower in type 2 diabetic patients compared with control subjects (P = 0.05). No significant effect of NO inhibition on myocardial perfusion during adenosine was found in any of the groups. In control subjects, alpha-receptor blockade increased hyperemic myocardial vascular resistance during NO inhibition, whereas no effect was observed in type 2 diabetic patients. At rest, a significant correlation was observed between rate-pressure product and myocardial perfusion in control subjects. NO inhibition and type 2 diabetes abolished this correlation. Endothelial and cardiac autonomic nerve function seems to play only a minimal role in the reduced hyperemic myocardial perfusion in type 2 diabetic patients. However, the linear correlation between resting perfusion and cardiac work appears to be abolished in type 2 diabetes and during NO synthase inhibition.
authors.affiliation: Department of Cardiology, Skejby Sygehus, Aarhus University Hospital, DK-8200 Aarhus N, Denmark. mette.marie@dadlnet.dk
authors.forename: Mette M
authors.initials: MM
authors.lastname: Madsen
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Søndergaard
authors.forename: Morten
authors.initials: M
authors.lastname: Bøttcher
authors.forename: Niels H
authors.initials: NH
authors.lastname: Buus
authors.forename: Ole
authors.initials: O
authors.lastname: Schmitz
authors.forename: Hans E
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Torsten T
authors.initials: TT
authors.lastname: Nielsen
mesh_terms: D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006940:Hyperemia; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010646:Phentolamine / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine