Abstract
In patients with congestive heart failure (CHF), β-receptor up-regulation is regarded as one of the mechanisms leading to improved function and prognosis. To clarify whether β-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 I receptor (AT1) antagonist on β-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, β-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 β-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, an ACE inhibitor that contains no sulthydryl group, but neither A-II nor the AT1 antagonist, also up-regulated β-receptors. The results suggest that β-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. (Jpn Circ J 1997; 61: 170 -179)
