Adrenergic stimulation of prostacyclin production in the rat tail artery. I. Response to agonists and antagonists.
The release of prostacyclin (PGI2) as measured by the production of 6-keto-PGF1 alpha was assessed in vitro in rat tail artery segments after exposure to norepinephrine (NE). Time course studies demonstrated a three fold increase in 6-keto-PGF1 alpha production in response to 6 X 10(-5) M NE that persisted for approximately one hour. This production was almost completely prevented by the cyclooxygenase inhibitors indomethacin and ibuprofen and the phospholipase inhibitor mepacrine. Vigorous rubbing of the vessel intima did not prevent the response to NE. Previously stimulated tissues were unresponsive to further addition of NE. However, the addition of arachidonic acid following NE resulted in further increases in PGI2 production which exceeded that of the addition of arachidonic acid alone. NE stimulation was significantly inhibited by phentolamine and prazosin pretreatment of the tissues but was not affected by yohimbine or propranolol. Alpha-1 adrenergic agonists (cirazoline, methoxamine, and phenylephrine) were stimulatory whereas alpha-2 agonists in high doses (tramazoline, BHT-920, xylazine, and UK-14304) were without effect. It is concluded that norepinephrine stimulates PGI2 production in the rat tail artery via an alpha-1 adrenergic receptor. NE also enhances the conversion of arachidonic acid to PGI2. Exhaustion of the response appears to be due to consumption of available arachidonic acid. The fact that procedures which generally remove most of the endothelium did not prevent NE-induced stimulation points to the vascular smooth muscle as the likely source of adrenergically mediated prostacyclin generation in this tissue.
Golub
M S
MS
Berger
M E
ME
Powell
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M
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013623:Tail; D014661:Vasoconstriction / Q000187:drug effects
D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001095:Arachidonic Acids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D009638:Norepinephrine