20-Hydroxyeicosatetraenoic acid is an endogenous vasoconstrictor of canine renal arcuate arteries
Autor: | Debebe Gebremedhin, John R. Falck, Yunn-Hwa Ma, Bettie Sue Siler Masters, Richard J. Roman, Joan E. Clark, David R. Harder, Michal L. Schwartzman |
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Rok vydání: | 1993 |
Předmět: |
medicine.medical_specialty
Potassium Channels Vascular smooth muscle Physiology Renal cortex Myogenic contraction Vasodilation Biology Kidney Muscle Smooth Vascular Membrane Potentials chemistry.chemical_compound Dogs Renal Artery Pregnancy Internal medicine Hydroxyeicosatetraenoic Acids medicine Animals Vasoconstrictor Agents Arachidonic Acid Dose-Response Relationship Drug 20-Hydroxyeicosatetraenoic acid Endocrinology medicine.anatomical_structure chemistry Circulatory system cardiovascular system Calcium Female lipids (amino acids peptides and proteins) Arachidonic acid Endothelium Vascular Rabbits Cardiology and Cardiovascular Medicine circulatory and respiratory physiology |
Zdroj: | Circulation Research. 72:126-136 |
ISSN: | 1524-4571 0009-7330 |
DOI: | 10.1161/01.res.72.1.126 |
Popis: | Recent studies have indicated that renal arteries can produce 20-hydroxyeicosatetraenoic acid (20-HETE) and suggest the potential involvement of a P450 metabolite of arachidonic acid in the myogenic activation of canine renal arteries. In the present study, the effects of 20-HETE on isolated canine renal arcuate arteries were studied. Administration of 20-HETE to the bath or the lumen at concentrations of 0.01-1 microM produced a graded reduction in the diameter of these vessels. In contrast, 19(R)-HETE was a vasodilator, whereas 19(S)-HETE was relatively inactive. The vasoconstrictor response to 20-HETE was not altered by the cyclooxygenase inhibitor indomethacin, endoperoxide/thromboxane receptor antagonist SQ29548, or combined blockade of the cyclooxygenase, lipoxygenase, and P450 pathways using indomethacin, baicalein, and 7-ethoxyresorufin. The response to 20-HETE was associated with depolarization and a sustained increase in the intracellular calcium concentration in renal vascular smooth muscle cells. Patch-clamp studies indicated that 20-HETE significantly reduced mean open time, the open-state probability, and the frequency of opening of a 117-pS K+ channel recorded from renal vascular smooth muscle cells in the cell-attached mode. Microsomes prepared from the renal cortex of dogs produced 20-HETE and 20-carboxyarachidonic acid when incubated with [14C]arachidonic acid. These results indicate that 20-HETE is an endogenous constrictor of canine renal arcuate arteries. The vasoconstrictor response to 20-HETE resembles the myogenic activation of these vessels after elevations in transmural pressure and suggests a potential role for this substance in the regulation of renal vascular tone. |
Databáze: | OpenAIRE |
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