Adaptation of cardiac myosin and creatine kinase to chronic hypoxia: role of anorexia and hypertension.
The effects of chronic hypobaric hypoxia (CHH, 28 days, simulated altitude 5,500 m) on the cardiac expression of myosin heavy chain (MHC) and creatine kinase (CK) was studied in rat left (LV) and right (RV) ventricle. To separate the effects of hypoxia from its associated perturbations, anorexia and pulmonary hypertension (resulting in RV hypertrophy), CHH animals were compared with normoxic controls (C) and with rats restricted in food supply (pair fed, PF). In RV, the increased proportion of beta-MHC in CHH (20 +/- 3%) vs. C (7 +/- 2%, P < 0.01) and vs. PF (12 +/- 2%, P < 0.05) rats was mainly attributed to hypertension. In contrast, the higher beta-MHC of CHH (23 +/- 2%) vs. C (13 +/- 2%, P < 0.05) in LV was mainly ascribed to anorexia (PF = 21 +/- 3%, not significant). A major contribution of anorexia was also evidenced in the isozymic profile of CK; anorexia accounted for a 25% decrease in mito-CK specific activity in LV, whereas hypertension partly accounted for the threefold increase in BB-CK in RV. CHH specifically induced a twofold rise in LV BB-CK. This suggests that both the expression of slow myosin, improving the economy of contraction, and the changes in CK isozymic profile could provide a biochemical basis for the CHH resistance to ischemia.
Pissarek
M
M
Laboratoire de Cardiologie Cellulaire et Moléculaire, Institut National de la Santé et de la Recherche Médicale U-446, Université de Paris-Sud, Chatenay-Malabry, France.
Bigard
X
X
Mateo
P
P
Guezennec
C Y
CY
Hoerter
J A
JA
D000064:Acclimatization; D000263:Adenylate Kinase / Q000378:metabolism; D000531:Altitude; D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000503:physiopathology*; D002908:Chronic Disease; D003402:Creatine Kinase / Q000096:biosynthesis*; D003580:Cytochromes / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006352:Heart Ventricles; D006973:Hypertension / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007527:Isoenzymes; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000097:blood
D003580:Cytochromes; D007527:Isoenzymes; D014284:Triiodothyronine; D003576:Electron Transport Complex IV; D003402:Creatine Kinase; D000263:Adenylate Kinase; D018995:Myosin Heavy Chains