Effects of chronic in vivo administration of nitroglycerine on ACh-induced endothelium-dependent relaxation in rabbit cerebral arteries.
OBJECTIVE
In the setting of nitrate tolerance, endothelium-dependent relaxation is reduced in several types of peripheral vessels. However, it is unknown whether chronic in vivo administration of nitroglycerine modulates such relaxation in cerebral arteries.


METHODS
Isometric force and smooth muscle cell membrane potential were measured in endothelium-intact strips from rabbit middle cerebral artery (MCA) and posterior cerebral artery (PCA).


RESULTS
ACh (0.1-10 microM) concentration-dependently induced endothelium-dependent relaxation during the contraction induced by histamine in both MCA and PCA. Chronic (10 days) in vivo administration of nitroglycerine reduced the ACh-induced relaxation in PCA but not in MCA, in the presence of the cyclooxygenase inhibitor diclofenac (3 microM). In the presence of the NO-synthase inhibitor N (omega)-nitro-L-arginine (L-NNA, 0.1 mM) plus diclofenac, in MCA from both nitroglycerine-untreated control and -treated rabbits, ACh (0.1-10 microM) induced a smooth muscle cell hyperpolarization and relaxation, and these were blocked by the small-conductance Ca(2+)-activated K(+)-channel inhibitor apamin (0.1 microM), but not by the large- and intermediate-conductance Ca(2+)-activated K(+)-channel inhibitor charybdotoxin (0.1 microM). In contrast, in PCA, ACh (<3 microM) induced neither hyperpolarization nor relaxation under these conditions, suggesting that the endothelium-derived relaxing factor is NO in PCA, whereas endothelium-derived hyperpolarizing factor (EDHF) plays a significant role in MCA.


CONCLUSIONS
It is suggested that in rabbit cerebral arteries, the function of the endothelium-derived relaxing factor NO and that of EDHF may be modulated differently by chronic in vivo administration of nitroglycerine.
Watanabe
Y
Y
Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan. yoshiw@med.nagoya-cu.ac.jp
Kusama
N
N
Itoh
T
T
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D004008:Diclofenac; D019335:Nitroarginine; D005996:Nitroglycerin; D000109:Acetylcholine