BIVENTRICULAR DOWN-REGULATION OF BETA-ADRENERGIC RECEPTORS IN RIGHT VENTRICULAR HYPERTROPHY INDUCED BY MONOCROTALINE

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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) (60mg/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 nor-epinephrine (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<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<0.05). NE in the left ventricle (LV) tended to increase. but not a significant extent (p<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<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. At 2 weeks the dissociation constant (Kd) of the RV decreased significantly (p<0.01), but the Kd of the LV showed no significant difference vs the control. At 4 weeks. Kd of the ventricles in the M-treated rats showed no significant difference vs. the control. These observations suggest that during the development of RVH, beta-adrenergic receptors were down-regulated not only in the hypertrophic RV but also in non-hypertrophic LV.