Alpha1-adrenergic stimulation induces tolerance of cardiac myocytes
to hypoxia through induction and activation of manganese superoxide
dismutase.
Yamashita, Nobushige, Masashi Nishida, Shiro Hoshida, Junsuke
Igarashi, Nasatsugu Hori, Michihiko Tada, and Tsunehiko Kuzuya.
The First Department of Medicine, The Department of
Pathophysiology, Osaka University Medical School, 2-2 Yamadaoka,
Suita, Osaka, Japan 565
APStracts 3:0161H, 1996.
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
[mu]M) for 24 hr, the manganese superoxide dismutase (Mn-SOD) content
and activity in the cells were increased from 0.61 +/- 0.03 to 0.87
+/- 0.04 ([mu]g/dish), and 22 +/- 1 to 55 +/- 4 (U/dish),
respectively. The specific activity of Mn-SOD was also increased from
36 to 63 (U/[mu]g Mn-SOD protein) after the stimulation with NE.
Prazosin (2 [mu]M) abolished the increase in Mn-SOD activity (U/mg
total protein). Creatine kinase (CK)-release after hypoxia (pO2 = 7
mmHg; 3 hr)-reoxygenation (1 hr) from cells pretreated with NE in the
presence of propranolol and yohimbine for 24 hr was attenuated by 48%
compared to 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.
Received 1 February 1996; accepted in final form 3 April 1996.
APS Manuscript Number H95-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96