Open AccessSelective Muscarinic Alterations of Nitric Oxide-Mediated Relaxations by Neointima
Author(s) -
Guido R.Y. De Meyer,
Hidde Bult,
Herman Ag
Publication year - 1992
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199204002-00058
Subject(s) - neointima , muscarinic acetylcholine receptor , endothelium , nitric oxide , phenylephrine , vasodilation , medicine , sodium nitroprusside , endocrinology , chemistry , muscarinic acetylcholine receptor m3 , acetylcholine , nitric oxide synthase , anatomy , biophysics , cardiology , receptor , biology , blood pressure , restenosis , stent
During neointima formation, which is an early and essential step in the development of atherosclerosis, endothelium-independent relaxations (nitroglycerin, 3-morpholinosydnonimine) are preserved, whereas muscarinic endothelium-dependent relaxation becomes impaired. The present study was undertaken to determine the selectivity of this impairment. The neointima was induced by positioning a nonocclusive, soft silicone collar around the left carotid artery of rabbits. The contralateral artery served as a control. Seven days later, vascular rings were mounted in organ chambers, contracted with phenylephrine (0.35 microM), and cumulative dose-relaxation curves were made. Intima-bearing vessels were less sensitive to acetylcholine, confirming the original observation. In contrast, the dose-relaxation curves for substance P and for the calcium ionophore A23187 were not altered in the presence of neointima. The curve for ATP was even shifted to the left. These results suggest that the nitric oxide synthase: cyclic GMP system remains intact in intima-bearing vessels and that the diminished endothelium-dependent relaxations are due to a selective alteration of the muscarinic receptors.