Reduced hyperpolarization in endothelial cells of rabbit aortic valve following chronic nitroglycerine administration. 2005

Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
Department of Cellular and Molecular Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Kawasumi 1, Nagoya, Aichi 467-8601, Japan.

This study was undertaken to determine whether long-term in vivo administration of nitroglycerine (NTG) downregulates the hyperpolarization induced by acetylcholine (ACh) in aortic valve endothelial cells (AVECs) of the rabbit and, if so, whether antioxidant agents can normalize this downregulated hyperpolarization. ACh (0.03-3 microM) induced a hyperpolarization through activations of both apamin- and charybdotoxin-sensitive Ca2+-activated K+ channels (K(Ca)) in rabbit AVECs. The intermediate-conductance K(Ca) channel (IK(Ca)) activator 1-ethyl-2-benzimidazolinone (1-EBIO, 0.3 mM) induced a hyperpolarization of the same magnitude as ACh (3 microM). The ACh-induced hyperpolarization was significantly weaker, although the ACh-induced [Ca2+]i increase was unchanged, in NTG-treated rabbits (versus NTG-untreated control rabbits). The hyperpolarization induced by 1-EBIO was also weaker in NTG-treated rabbits. The reduced ACh-induced hyperpolarization seen in NTG-treated rabbits was not modified by in vitro application of the superoxide scavengers Mn-TBAP, tiron or ascorbate, but it was normalized when ascorbate was coadministered with NTG in vivo. Superoxide production within the endothelial cell (estimated by ethidium fluorescence) was increased in NTG-treated rabbits and this increased production was normalized by in vivo coadministration of ascorbate with the NTG. It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced hyperpolarization in rabbit AVECs, possibly through chronic actions mediated by superoxide.

UI MeSH Term Description Entries
D007476 Ionophores Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. Ionophore
D008297 Male Males
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002120 Calcium Channel Agonists Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture. Calcium Channel Activators,Calcium Channel Agonists, Exogenous,Calcium Channel Agonist,Exogenous Calcium Channel Agonists,Activators, Calcium Channel,Agonist, Calcium Channel,Agonists, Calcium Channel,Channel Activators, Calcium,Channel Agonist, Calcium,Channel Agonists, Calcium
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D005996 Nitroglycerin A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives. Glyceryl Trinitrate,Anginine,Dynamite,Gilustenon,Nitrangin,Nitro-Bid,Nitro-Dur,Nitrocard,Nitroderm,Nitroderm TTS,Nitroglyn,Nitrol,Nitrolan,Nitrong,Nitrospan,Nitrostat,Perlinganit,Susadrin,Sustac,Sustak,Sustonit,Transderm Nitro,Tridil,Trinitrin,Trinitrolong,Nitro Bid,Nitro Dur,NitroBid,NitroDur,Trinitrate, Glyceryl
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine

Related Publications

Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
October 2005, British journal of pharmacology,
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
July 2012, Clinical and experimental pharmacology & physiology,
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
January 1999, British journal of pharmacology,
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
October 2005, British journal of pharmacology,
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
March 1988, Proceedings of the National Academy of Sciences of the United States of America,
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
September 1994, Thrombosis research,
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
October 1984, International journal of radiation oncology, biology, physics,
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
April 1987, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.),
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
September 1969, The Journal of thoracic and cardiovascular surgery,
Nobuyoshi Kusama, and Junko Kajikuri, and Tamao Yamamoto, and Yoshimasa Watanabe, and Yoshikatsu Suzuki, and Hirotada Katsuya, and Takeo Itoh
June 1997, Naunyn-Schmiedeberg's archives of pharmacology,
Copied contents to your clipboard!