Alpha 1-adrenergic stimulation induces cardiac tolerance to hypoxia via induction and activation of Mn-SOD.
We examined whether or not alpha 1-adrenergic stimulation increases the tolerance of the heart to ischemia using a hypoxia-reoxygenation model of cardiac myocytes. After exposure to norepinephrine (NE; 0.2 microM) for 24 h, the manganese superoxide dismutase (Mn-SOD) content and activity in the cells were increased from 0.61 +/- 0.03 to 0.87 +/- 0.04 microgram/dish and 22 +/- 1 to 55 +/- 4 U/dish, respectively. The specific activity of Mn-SOD was also increased from 36 to 63 U/microgram Mn-SOD protein after the stimulation with NE. Prazosin (2 microM) abolished the increase in Mn-SOD activity (U/mg total protein). Creatine kinase (CK) release after hypoxia (PO2 7 mmHg; 3 h)-reoxygenation (1 h) from cells pretreated with NE in the presence of propranolol and yohimbine for 24 h was attenuated by 48% compared with that from cells without NE stimulation. When antisense oligodeoxyribonucleotides to Mn-SOD were added to myocyte cultures, the increase in Mn-SOD activity (U/mg total protein) and the attenuation of CK release after the addition of NE in the presence of propranolol and yohimbine were not observed. These results suggest that alpha 1-adrenergic stimulation increases the tolerance of myocytes to hypoxia through induction and activation of Mn-SOD.
First Department of Medicine, Osaka University Medical School, Japan.
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N
Yamashita
M
M
Nishida
S
S
Hoshida
J
J
Igarashi
M
M
Hori
T
T
Kuzuya
M
M
Tada
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation; D004790:Enzyme Induction; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000201:enzymology*; D019157:Ischemic Preconditioning, Myocardial; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D013482:Superoxide Dismutase; D009638:Norepinephrine