Effects of 2-deoxyglucose, a metabolic inhibitor, on spontaneous contraction and adrenoceptor responsiveness in cultured rat ventricular myocytes.
Although it is well known that myocardial ischemia induces the depletion of myocardial ATP and sustained myocardial dysfunction, the mechanisms causing impaired myocardial function have not been elucidated completely. To clarify the relationship between ATP depletion and myocardial contractility, we investigated the influence of myocardial ATP depletion on spontaneous beating in cultured rat ventricular myocytes. Furthermore, because catecholamines have been used to improve myocardial contraction in the ischemic heart, we attempted to determine whether the ATP depletion per se alters the contractile responses to alpha 1- and beta-adrenoceptor stimulation. After 24 hr of culture in the presence of a metabolic inhibitor, 2-deoxyglucose (2DG, 5mM), myocardial contractility decreased to 19% of the vehicle level, and returned to normal after the removal of 2DG. The beating rate did not show any alterations in the vehicle, in the presence of 2DG (2DG [+/+]) or after the removal of 2DG (2DG [+/-]). Norepinephrine (NE) caused significant decreases in beating rate and increases in contractility in all groups. Isoproterenol (ISP) caused significant increases in beating rate and contractility in all groups. In the 2DG (+/+) group, the contractility was significantly lower as compared to other groups during NE or ISP stimulation. However, the percent change of contractility was similar to those of other groups after NE or ISP stimulation in the 2DG (+/+) group. These results suggest that decreased myocardial ATP causes the decreased contractility and does not affect the alpha 1- or beta-adrenoceptor-mediated responses.
Kanaya
N
N
Department of Anesthesiology, Sapporo Medical University School of Medicine, Japan.
Miyamoto
A
A
Kimura
H
H
Kawana
S
S
Namiki
A
A
Ohshika
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000963:Antimetabolites; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D007545:Isoproterenol; D009638:Norepinephrine