title: Attenuation of changes in sarcoplasmic reticular gene expression in cardiac hypertrophy by propranolol and verapamil.
abstract: The effects of propranolol and verapamil on contractile dysfunction, subcellular remodeling and changes in gene expression in cardiac hypertrophy due to pressure overload were examined. Rats were subjected to banding of the abdominal aorta and then treated with either propranolol (10 mg/kg daily), verapamil (5 mg/kg daily) or vehicle for 8 weeks after the surgery. Depression of the left ventricular function in the hypertrophied heart was associated with decreases in myofibrillar and myosin Ca2+ ATPase activities as well as Ca2+-pump and Ca2+-release activities of the sarcoplasmic reticulum (SR). The level of alpha-myosin heavy chain (alpha-MHC) mRNA was decreased while that of beta-MHC mRNA was increased in the pressure-overloaded heart. The level of SR Ca2+-pump ATPase (SERCA2) mRNA and protein content for SERCA2 were decreased in the pressure overloaded heart. Treatment of the hypertrophied animals with propranolol or verapamil resulted in preservation of the left ventricular function and prevention of the subcellular alterations. Shift in the alpha- and beta-MHC mRNA levels and changes in the expression in SERCA2 mRNA level and protein content were also attenuated by these treatments. The results suggest that blockade of beta-adrenoceptors or voltage-dependent calcium channels normalizes the cardiac gene expression, prevents subcellular remodeling and thus attenuates heart dysfunction in rats with cardiac hypertrophy. Furthermore, both cardiac beta-adrenoceptors and L-type Ca2+-channels may be involved in the genesis of cardiac hypertrophy due to pressure overload.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Manitoba, Winnipeg, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Takeo
authors.forename: A B
authors.initials: AB
authors.lastname: Elmoselhi
authors.forename: R
authors.initials: R
authors.lastname: Goel
authors.forename: E
authors.initials: E
authors.lastname: Sentex
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: N S
authors.initials: NS
authors.lastname: Dhalla
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology; D015870:Gene Expression; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction; D009218:Myosins / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D020257:Ventricular Remodeling; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D009124:Muscle Proteins; D012333:RNA, Messenger; D011433:Propranolol; D014700:Verapamil; D000251:Adenosine Triphosphatases; D009218:Myosins; D002118:Calcium