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.
Yonemochi
H
H
Department of Laboratory Medicine, Oita Medical University, Japan.
Saikawa
T
T
Yasunaga
S
S
Iwao
T
T
Takakura
T
T
Nakagawa
M
M
Sakata
T
T
Ito
M
M
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011943:Receptors, Adrenergic, beta; D013777:Tetrazoles; D000804:Angiotensin II; D002216:Captopril; C081643:candesartan