Effects of K+ channel openers on relaxations to nitric oxide and endothelium-derived hyperpolarizing factor in rat mesenteric artery. 1998

R White, and C R Hiley
Department of Pharmacology, University of Cambridge, UK.

Relaxation of methoxamine-precontracted, endothelium-intact, rat mesenteric artery in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) and indomethacin (10 microM) is attributed to endothelium-derived hyperpolarizing factor (EDHF). The potency of carbachol in the presence (but not the absence) of L-NAME was reduced by levcromakalim and pinacidil, activators of ATP-sensitive K+ channels (KATP). EDHF-mediated relaxation to Ca2+ ionophore A23187 was unaffected by these compounds but was inhibited by verapamil at the level of the smooth muscle. Levcromakalim and pinacidil had the same effects at both reduced and standard levels of tone. Glibenclamide (10 microM), a KATP blocker, alone did not affect carbachol relaxations but abolished both relaxation to levcromakalim and pinacidil and their inhibitory action on EDHF released by carbachol. Levcromakalim inhibited the endothelium-dependent hyperpolarization of mesenteric arteries to carbachol but not to A23187. Thus, levcromakalim or pinacidil inhibit EDHF, but not nitric oxide, release by carbachol through an action on the endothelium.

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
D008638 Mesenteric Arteries Arteries which arise from the abdominal aorta and distribute to most of the intestines. Arteries, Mesenteric,Artery, Mesenteric,Mesenteric Artery
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
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums

Related Publications

R White, and C R Hiley
January 1993, American journal of respiratory cell and molecular biology,
R White, and C R Hiley
October 1997, Prostaglandins, leukotrienes, and essential fatty acids,
Copied contents to your clipboard!