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      Antihypertensive effect of all-cis-5,8,11,14,17-icosapentaenoate of aged rats is associated with an increase in the release of ATP from the caudal artery.

      Journal of Vascular Research
      Adenine Nucleotides, blood, Adenosine, Adenosine Triphosphate, metabolism, Aging, physiology, Animals, Antihypertensive Agents, pharmacology, Arteries, drug effects, Blood Pressure, Body Weight, Cholesterol, Eating, Eicosapentaenoic Acid, Fatty Acids, Female, Lipids, Purines, Rats, Rats, Wistar

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          Abstract

          Fish oils have been shown to lower blood pressure in hypertensive subjects. All-cis-5,8,11,14,17-icosapentaenoate (EPA), one of the omega-3 polyunsaturated fatty acids, is known to be one of the major active components in fish oil that has beneficial effects on the cardiovascular system. However, little is known about the antihypertensive effect of EPA alone on blood pressure. In the present study, we have determined the spontaneous and noradrenaline-evoked release of ATP, ADP, AMP, and adenosine from caudal arteries of aged (100 weeks old) Wistar rats which were fed a standard diet or a high cholesterol diet, treated with EPA. Dietary EPA administration increased plasma and caudal arterial EPA concentrations and repressed increases in blood pressure with advancing age in both aged rats with and without hypercholesterolemia. In addition, noradrenaline (1 micromol/l) evoked a significantly greater release of purines from the caudal arteries of EPA-administered aged rats compared to both sets of control rats. Regression analysis revealed a significant relationship between the total amount of purines released from the artery and blood pressure. These results suggest that administration of EPA to aged rats increases the release of ATP from the vascular endothelial cells, leading to repression of the blood pressure rise seen with advancing age.

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          Participation by purines in the modulation of norepinephrine release by methoxamine

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            Simultaneous determination of nerve-induced adenine nucleotides and nucleosides released from rabbit pulmonary artery.

            Electrical field stimulation elicits the release of catecholamines, adenine nucleotides, and adenosine from the rabbit pulmonary artery in a frequency dependent manner. To enhance our ability to investigate the release of endogenous adenine nucleotides and adenosine from this and other biological preparations, a new analytical procedure has been developed. This procedure involves the use of an internal standard, 9-beta-D-arabinofuranosyladenine (IS), the derivatization of ATP, ADP, AMP, adenosine (Ado), and IS with chloroacetaldehyde, the isocratic high-performance liquid chromatographic separation of these ethenopurine derivatives on an Ultron N-phenyl HPLC column, and their detection and quantitation by fluorescence spectroscopy. This procedure has enhanced sensitivity and reliability over existing procedures due to the stability of the chromatographic baseline and the use of an internal standard. When this analytical procedure was utilized to measure the adenine nucleotides and Ado that are released from the rabbit pulmonary artery in response to electrical field stimulation, it was observed that the release of endogenous ATP, ADP, AMP, and Ado exceeded that of endogenous norepinephrine. A molar ratio (6-amino purines:catecholamines) of approximately 2000:1 was obtained at a stimulation frequency of 16 Hz. This observation suggests an important extracellular role for adenine nucleotides and nucleosides in the physiology of vascular tissues.
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              Eicosapentaenoic Acid Enhances Intracellular Free Calcium in Cultured Human EndothelialCells

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