An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide.
Myogenic tone is an important determinant of vascular tone and blood flow in small resistance arteries of certain vascular beds. The role of the endothelium in myogenic responses is unclear. We hypothesized that endothelium-derived NO release modulates myogenic constriction in small resistance arteries and that mesenteric small arteries from mice with targeted disruption of the gene for endothelial NO synthase (eNOS) (knockout mice) demonstrate greater myogenic tone than do wild-type mice. Third-order mesenteric arteries (approximately 200 micrometer) were isolated and mounted in a pressure myograph. Internal diameter was recorded over a pressure range of 10 to 80 mm Hg. Removal of the endothelium significantly (P<0.05) enhanced the magnitude of myogenic constriction in wild-type mice. Similarly, pretreatment of arteries with N(G)-nitro-L-arginine methyl ester (L-NAME; 300 micromol/L) produced a comparable significant (P<0.05) increase in myogenic tone, whereas indomethacin (5 micromol/L) had no effect. eNOS knockout arteries also exhibited myogenic constriction. Neither L-NAME nor indomethacin had any effect on myogenic tone in the arteries of eNOS knockout mice. However, blockade of potential endothelium-derived hyperpolarizing factor-like mechanisms via inhibition of K(+) flux using either apamin (100 nmol/L) with charybdotoxin (100 nmol/L), Ba(2+) (30 micromol/L) with ouabain (1 mmol/L), or 18alpha- glycyrrhetinic acid (100 micromol/L) significantly (P<0.01) enhanced myogenic constriction. This study demonstrates that basal endothelium- derived NO modulates myogenic tone in mesenteric small arteries of wild- type mice. However, eNOS knockout arteries display normal myogenic responsiveness despite the absence of basal NO activity. The data suggest that this compensatory effect is due to the activity of an endothelium-derived hyperpolarizing factor to normalize vascular tone
|Title:||An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide|
|Additional information:||UI - 21521251 LA - eng RN - 0 (Biological Factors) RN - 0 (Enzyme Inhibitors) RN - 0 (Nitric Oxide Donors) RN - 0 (Potassium Channel Blockers) RN - 0 (S-nitro-N-acetylpenicillamine) RN - 0 (Vasoconstrictor Agents) RN - 0 (endothelium-dependent hyperpolarization factor) RN - 10102-43-9 (Nitric Oxide) RN - 115422-61-2 (Charybdotoxin) RN - 1449-05-4 (18alpha-glycyrrhetinic acid) RN - 24345-16-2 (Apamin) RN - 471-53-4 (Glycyrrhetinic Acid) RN - 50903-99-6 (NG-Nitroarginine Methyl Ester) RN - 52-67-5 (Penicillamine) RN - 53-86-1 (Indomethacin) RN - 7440-39-3 (Barium) RN - 7440-70-2 (Calcium) RN - 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13- dienoic Acid) RN - EC 1.14.13.- (endothelial constitutive nitric oxide synthase) RN - EC 126.96.36.199 (Nitric-Oxide Synthase) PT - Journal Article DA - 20011019 IS - 1524-4563 SB - IM CY - United States|
|Keywords:||15-Hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5, 13-dienoic Acid, ABSENCE, ACID, activity, AGENT, AGENTS, analogs & derivatives, Animal, antagonists & inhibitors, APAMIN, Arteries, artery, Barium, BED, beds, Biological Factors, BLOCKADE, Blood, blood flow, BLOOD-FLOW, calcium, channel, Charybdotoxin, clinical, Constriction, DETERMINANT, Diameter, Disruption, DO, DONOR, DONORS, drug effects, EC, Endothelial, Endothelium, Endothelium, Vascular, enhanced, enzyme, Enzyme Inhibitors, factors, Female, flow, GENE, genetics, Genotype, Glycyrrhetinic Acid, IM, in vitro, INCREASE, Indomethacin, inhibition, INHIBITOR, INHIBITORS, internal, knockout, knockout mice, L-NAME, LA, Male, MECHANISM, mechanisms, Mesenteric Arteries, metabolism, mice, Mice, Inbred C57BL, Mice, Knockout, MM, NG-Nitroarginine Methyl Ester, nitric oxide, Nitric Oxide Donors, nitric oxide synthase, NITRIC-OXIDE, Nitric-Oxide Synthase, Ouabain, OXIDE, Penicillamine, pharmacology, physiology, Potassium, POTASSIUM CHANNEL, Potassium Channel Blockers, Pressure, RANGE, release, Removal, Resistance, response, RESPONSES, RESPONSIVENESS, Role, small, STATE, STATES, Support, Non-U.S.Gov't, SYNTHASE, TARGETED DISRUPTION, tone, united, United States, UNITED-STATES, vascular, Vascular Resistance, VASCULAR TONE, vasoconstriction, VASOCONSTRICTOR, Vasoconstrictor Agents, WILD-TYPE|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
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