Lack of interaction of angiotensin converting enzyme inhibitors with muscarinic and neuropeptide Y receptors.
In studies conducted in patients undergoing cardiac catheterizations, some hemodynamic changes were observed after the acute sublingual administration of the angiotensin converting enzyme inhibitors (ACEI) captopril, enalapril, and lisinopril. These changes consisted of an increase in pulmonary artery pressure, pulmonary vascular resistance (PVR) and induction of hypoxia. The pressure changes were transitory and disappeared after 25 min. The possible mechanisms involved in these changes may relate to interactions of the ACEI with peripheral receptor systems for hormones and neurotransmitters. We have thus undertaken the task of evaluating the potential effect of ACEI on biological receptor molecules. We have begun with studies on muscarinic receptors, and the recently characterized neuropeptide Y (NPY) receptors of endothelial cells. Equilibrium binding assays with 3H-QNB have been conducted for muscarinic receptors using rat brain synaptosomes, due to its expression of multiple muscarinic receptors subtypes. In addition 125BH-NPY binding assays were conducted on intact adrenal medullary endothelial cells. Enalapril and captopril, 10(-7) to 10(-3) M, were not able to produce significant inhibition of either muscarinic or NPY receptor probes. The paradoxical changes elicited by sublingual ACEI seems not to involve interaction with muscarinic or NPY receptors.
Department of Pharmacology, Universidad Central del Caribe, School of Medicine, Bayamón, Puerto Rico 00621-6032.
W I
WI
Silva
P
P
Sanabria
P I
PI
Altieri
D000313:Adrenal Medulla / Q000098:blood supply; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000187:drug effects*; D013574:Synaptosomes / Q000737:chemistry / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011976:Receptors, Muscarinic; D017476:Receptors, Neuropeptide Y; D011813:Quinuclidinyl Benzilate