Nicotine-evoked cytosolic Ca2+ increase and cell depolarization in capillary endothelial cells of the bovine adrenal medulla

Endothelial cells are directly involved in many functions of the cardiovascular system by regulating blood flow and blood pressure through Ca2+ dependent exocitosis of vasoactive compounds. Using the Ca2+ indicator Fluo-3 and the patch-clamp technique, we show that bovine adrenal medulla capillary endothelial cells (B AMCECs) respond to acetylcholine (ACh) with a cytosolic Ca2+ increase and depolarization of the membrane potential (20.3±0.9 mV; n=23). The increase in cytosolic Ca2+ induced by 10µM ACh was mimicked by the same concentration of nicotine but not by muscarine and was blocked by 100 µM of hexamethonium. On the other hand, the increase in cytosolic Ca2+ could be depressed by nifedipine (0.01 -100 µM) or withdrawal of extracellular Ca2+. Taken together, these results give evidence for functional nicotinic receptors (nAChRs) in capillary endothelial cells of the adrenal medulla. It suggests that nAChRs in B AMCECs may be involved in the regulation of the adrenal gland's microcirculation by depolarizing the membrane potential, leading to the opening of voltage-activated Ca2+ channels, influx of external Ca2+ and liberation of vasoactive compounds.

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