title: Characteristics of attenuated endothelium-dependent relaxation seen in rabbit intrapulmonary vein following chronic nitroglycerine administration.
abstract: 1 This study was undertaken to determine whether long-term in vivo administration of nitroglycerine (NTG) downregulates the endothelium-dependent relaxation induced by acetylcholine (ACh) in the rabbit intrapulmonary vein and, if so, whether the type 1 angiotensin II receptor (AT(1)R) blocker valsartan normalizes this downregulated relaxation. 2 In strips treated with the cyclooxygenase inhibitor diclofenac, ACh induced a relaxation only when the endothelium was intact. A small part of this ACh-induced relaxation was inhibited by coapplication of two Ca(2+)-activated K(+)-channel blockers (charybdotoxin (CTX)+apamin) and the greater part of the response was inhibited by the nitric-oxide-synthase inhibitor N(omega)-nitro-L-arginine (L-NNA). 3 The endothelium-dependent relaxation induced by ACh, but not the endothelium-independent relaxation induced by the nitric oxide donor NOC-7, was significantly reduced in NTG-treated rabbits (versus those in NTG-nontreated control rabbits). The attenuated relaxation was normalized by coapplication of valsartan with the NTG. 4 In the vascular wall, both the amount of localized angiotensin II and the production of superoxide anion were increased by in vivo NTG treatment. These variables were normalized by coapplication of valsartan with the NTG. 5 It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced endothelium-dependent relaxation, mainly through an inhibition of endothelial nitric oxide production in the rabbit intrapulmonary vein. A possible role for AT(1)R is proposed in the mechanism underlying this effect.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kusama
authors.forename: Junko
authors.initials: J
authors.lastname: Kajikuri
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hirotada
authors.initials: H
authors.lastname: Katsuya
authors.forename: Takeo
authors.initials: T
authors.lastname: Itoh
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000809:Angiotensins / Q000096:biosynthesis; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004347:Drug Interactions; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000502:physiology*; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D011667:Pulmonary Veins / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C115239:3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine; D047228:Angiotensin II Type 1 Receptor Blockers; D000809:Angiotensins; D002121:Calcium Channel Blockers; D006834:Hydrazines; D020030:Nitric Oxide Donors; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014665:Vasodilator Agents; D013481:Superoxides; D018999:Charybdotoxin; D019335:Nitroarginine; D001030:Apamin; D000068756:Valsartan; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D014633:Valine