Angiotensin-converting enzyme inhibitor up-regulates cardiac beta-receptors in cultured neonatal rat myocytes.

In patients with congestive heart failure (CHF), beta-receptor up-regulation is regarded as one of the mechanisms leading to improved function and prognosis. To clarify whether beta-receptor up-regulation is involved in the mechanisms underlying the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors, we investigated the actions of ACE inhibitors and an angiotensin II type 1 receptor (AT1) antagonist on beta-receptors of neonatal rat cultured cardiac myocytes. Angiotensin II (A-II) increased the spontaneous beating frequency of the cells, and the effect was completely antagonized by the AT1 antagonist CV-11974. Under control conditions, beta-receptor density (Bmax) and affinity (Kd) were measured by radiobinding assay with the hydrophilic ligand [3H]CGP-12177, and were 103 +/- 11 fmol/mg protein and 3.4 +/- 0.4 nmol/L, respectively. Captopril increased the beta-receptor density of myocytes and augmented the response to isoproterenol. Bmax was increased by 34% after 24 h treatment with 10(-6) mol/L captopril. CV-3480, and ACE inhibitor that contains no sulfhydryl group, but neither A-II nor the AT1 antagonist, also up-regulated beta-receptors. The results suggest that beta-receptor up-regulation contributes at least partly to the beneficial cardiac effects of ACE inhibitors in patients with CHF. ACE inhibitors and AT1 antagonists seem to play different roles in clinical practice.