Biventricular down-regulation of beta-adrenergic receptors in right ventricular hypertrophy induced by monocrotaline.
To investigate the changes in beta-adrenergic receptors in the right and left ventricles during the development of cardiac hypertrophy, right ventricular hypertrophy (RVH) was induced in rats by a single injection of monocrotaline (M) (60 mg/kg). The rats demonstrated RVH at 2 weeks and severe RVH with congestive heart failure at 4 weeks after the injection. Changes in the beta-adrenergic receptors in the membrane fractions of both ventricles were examined in the M-treated vs. control rats using 125I-iodocyanopindolol (ICYP). Plasma and tissue catecholamines were measured. Plasma levels of norepinephrine (NE) and epinephrine (EP) showed no change at 2 weeks after the injection. However, at 4 weeks there was a significant increase in NE (p less than 0.01), but not in EP. There was no significant change in NE or EP in either ventricle at 2 weeks vs. the controls. However, at 4 weeks there was a significant increase in both NE and EP in the right ventricle (RV) (p less than 0.05). NE in the left ventricle (LV) tended to increase, but not a significant extent (p less than 0.1). With the development of RVH at 2 weeks, the maximum number of binding sites (Bmax) in both the RV and LV showed a significant decrease (p less than 0.01). There was a 21% decrease of Bmax in the RV and 15% in the LV at 2 weeks vs. the controls. At 4 weeks, the changes in Bmax were more prominent, with a 57% decrease in the RV and 22% in the LV.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishikawa
S
S
4th Department of Internal Medicine, Shimane Medical University, Japan.
Honda
M
M
Yamada
S
S
Morioka
S
S
Moriyama
K
K
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D015536:Down-Regulation; D004837:Epinephrine / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D016686:Monocrotaline; D009638:Norepinephrine; D004837:Epinephrine