β-Adrenergic System Is Modified in Compensatory Pressure Cardiac Overload in Rats

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Abstract
Summary: The β-adrenergic system has been explored in cardiac hypertrophy (CH) by combining an in vitro study of the inotropic effect of isoproterenol (ISO) and of fors-kolin (FSK) and binding assays using radioactive pindolol. C'H was obtained within 4–6 weeks by banding the abdominal aorta which results in an increase in left ventricular (LV) weight [743 + 14 and 1.098 ± 24 mg in sham-operated (SH) and in CH. respectively, p < 0.011 and in the LV wt/body wt ratio (2.14 +0.05 and 3.24 + 0.05. p< 0.001). The inotropic effect was evaluated on an isolated Langendorff heart preparation whose coronary How was normalized per gram of tissue either by using different constant coronary pressures (75 and 110 mm Hg in SH and in CH, respectively) or different constant coronary Hows (15 and 20 ml min−1 in SH and CH. respectively). Binding assays were performed using l25 I pindolol, a rather crude preparation of sarcolemma and a LKjAND program for calculation, (i) The inotropic responsiveness to both ISO and FSK is depressed by 30% in CH. at any drug concentration, without change in EC50 whatever the technique used to perfuse the tissue. The time course of the process is slower but, in the case of ISO, remains biphasic. (ii) Binding assays show a normal affinity (Kd 100 pM) while receptor density is depressed (32 + 3 and 25 ± 2 fmol mg protein−1, p < 0.05 or 3,287 ± 312 and 2,000 ± 163 fmol/g fresh tissue, p < 0.01, in SH and CH. respectively). The total number of receptors per LV is unchanged. In conclusion: (i) the inotropic response to β agonist is impaired in compensated CH in rat: and (ii) this impairment is not entirely explained by a change in β receptors whose total number per LV remains unmodified in spite of a diminution of its density. In addition, the inotropic response to FSK, an activator of the C subunit of adenylate cyclase, is also depressed suggesting a change at a postreceptor level.

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