Biomaterial Database

Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP-sensitive potassium channels. 1995

M E Murphy, and J E Brayden

Department of Pharmacology, College of Medicine, University of Vermont Medical Research Facility, Colchester 05446, USA.

1. Nitric oxide (NO) relaxes vascular smooth muscle (VSM) by mechanisms which are not fully understood. One possibility is that NO hyperpolarizes membranes, thereby diminishing Ca2+ entry through voltage-dependent Ca2+ channels. In the current study, the effects of NO on membrane potential of rabbit mesenteric arteries were recorded using intracellular microelectrodes. 2. NO, released by 3-morpholinosydnonimine (SIN-1, 3 microM), reversibly hyperpolarized arteries by -9.5 +/- 4.0 mV (means +/- S.D., n = 97) from a resting membrane potential of -53.1 +/- 5.7 mV. The hyperpolarization was blocked by oxyhaemoglobin (20 microM), and only occurred in arteries pre-treated with N omega-nitro-L-arginine (100 microM) or denuded of endothelium. 3. The effect of SIN-1 was concentration dependent (EC50 approximately 0.4 microM) and its dose response was shifted to the left by zaprinast (100 microM), an inhibitor of cGMP-specific phosphodiesterases. 4. The hyperpolarization due to SIN-1 was modified by changes in extracellular K+ concentration, but not by changes in Ca2+, Na+ or Cl-. The hyperpolarization was blocked by glibenclamide (IC50 approximately 0.15 microM), but not by apamin (3-300 nM), barium (5-150 microM), tetraethylammonium (0.1-10 mM), or 4-aminopyridine (5-500 microM). The hyperpolarization due to lemakalim (0.03-3 microM), an activator of ATP-sensitive potassium channels (KATP), displayed the same sensitivities to these K+ channel blocking agents, whereas the endothelium-derived hyperpolarizing factor, triggered by the addition of acetylcholine (3 microM), caused a hyperpolarization (-15.3 +/- 6.2 mV) that was blocked by apamin, but not by any other agent. 5. These results suggest that NO hyperpolarizes VSM in rabbit mesenteric arteries by activating KATP channels, with the accumulation of cGMP as an intermediate step.

UI	MeSH Term	Description	Entries
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
D008638	Mesenteric Arteries	Arteries which arise from the abdominal aorta and distribute to most of the intestines.	Arteries, Mesenteric,Artery, Mesenteric,Mesenteric Artery
D008839	Microelectrodes	Electrodes with an extremely small tip, used in a voltage clamp or other apparatus to stimulate or record bioelectric potentials of single cells intracellularly or extracellularly. (Dorland, 28th ed)	Electrodes, Miniaturized,Electrode, Miniaturized,Microelectrode,Miniaturized Electrode,Miniaturized Electrodes
D008981	Molsidomine	A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS.	Morsydomine,Corpea,Corvaton,Duracoron,Fali-Cor,Korvatone,MTW-Molsidomin,Molsi 1A Pharma,Molsi-AZU,Molsi-Puren,Molsibeta,Molsicor,Molsidain,Molsidomin,Molsidomin Heumann,Molsidomin Stada,Molsidomin Von Ct,Molsidomin-Ratiopharm,Molsihexal,Molsiket,SIN-10,Sydnopharm,Fali Cor,Heumann, Molsidomin,MTW Molsidomin,Molsi AZU,Molsi Puren,Molsidomin Ratiopharm,SIN 10,SIN10,Von Ct, Molsidomin
D009126	Muscle Relaxation	That phase of a muscle twitch during which a muscle returns to a resting position.	Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
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
D005905	Glyburide	An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide	Glibenclamide,Daonil,Diabeta,Euglucon 5,Euglucon N,Glybenclamide,HB-419,HB-420,Maninil,Micronase,Neogluconin,HB 419,HB 420,HB419,HB420
D000255	Adenosine Triphosphate	An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.	ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2