Myosin heavy chain isoforms expression and cyclic AMP concentrations in hypoxia-induced hypertrophied right ventricle in rats.
We have previously demonstrated that the relative expression of myosin heavy chain-beta (MHC-beta) in both ventricles of rats exposed to long-term hypobaric hypoxia correlated significantly with the relative ventricular mass. In the present study, we investigated whether an increased expression of MHC-beta was accompanied by a reduction in cyclic AMP (cAMP) activity in hypoxia-induced hypertrophied right ventricle (RV). We used male Wistar-Kyoto rats born and raised at simulated altitudes (2200 m: H2 group or 4000 m: H4 group) compared to age-matched sea level controls (SC group). There were no significant differences between the groups in basal and forskolin-stimulated adenylyl cyclase (AC) activities. The basal and IBMX-inhibited phosphodiesterase (PDE) activities were slightly higher in both hypoxic groups (p>0.05), except that the H2 group had a higher basal PDE activity than the SC group (p<0.05). The AC/PDE activity ratios were significantly decreased in both hypoxic groups (p<0.05), suggesting that low concentrations of cellular cAMP were maintained in the RV under hypoxic conditions. However, there were no correlations between MHC-beta expression and either AC activity, PDE activity, or AC/PDE activity ratio. These results provided evidence against the causal role for cAMP concentration in the expression of MHC-beta associated with hypoxia-induced ventricular hypertrophy.
Department of Environmental Physiology, Graduate School of Human and Environmental Studies, Kyoto University, Yoshida, Sakyo, Kyoto 606-8501, Japan.
Takeshi
T
Hashimoto
Atsushi
A
Sugiyama
Sadayoshi
S
Taguchi
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000531:Altitude; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D017380:Hypertrophy, Right Ventricular / Q000473:pathology*; D000860:Hypoxia; D018995:Myosin Heavy Chains / Q000096:biosynthesis* / Q000737:chemistry*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D020033:Protein Isoforms; D051381:Rats; D011921:Rats, Inbred WKY
D010726:Phosphodiesterase Inhibitors; D020033:Protein Isoforms; D005576:Colforsin; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D018995:Myosin Heavy Chains; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine