Endothelium-dependent vasorelaxation induced by Cn-acetal plasmalogens.
In this study the effects of the synthetic acetal plasmalogens (AP) C17-AP, C13-AP, C9-AP on isolated rabbit aorta were investigated with emphasis on their putative relationship with endothelium-dependent relaxing factor (EDRF). The various AP were obtained by total synthesis from the related fatty acid chlorides. In isolated rabbit aorta precontracted with phenylephrine (PE, 10(-7) M), C17-AP (greater than 10(-6) M) and C13-AP (greater than 10(-5) M) exerted an endothelium-dependent relaxation (EDR). In contrast, C9-AP was totally devoid of effect. Given 30 or 45 min before PE, C17-AP (greater than 10(-6) M) and C13-AP (greater than 10(-5) M) abolished the carbachol-induced ERD; moreover, following preincubation with C17-AP, enhanced contraction was obtained with carbachol. Similar effects were obtained with preincubation of aortas with both AA(10(-4) M) and A 23 187 (10(-8) M). Conversely preincubation of aortas with carbachol (3X 10(-6) M) and ATP (3 X 10(-5) M) did not significantly modify the carbachol-induced EDR. Atropine (3 X 10(-7) M) did not affect the relaxation induced by C17-AP and C13-AP. The in vivo effects are correlated with the in vitro actions of acetal plasmalogens: C17-AP and C13-AP but not C9-AP, given iv (5 mg/kg) induced a pronounced but transient hypotension which lasted 2-3 min and which was followed by a persistent hypertensive state. Atropine (0.5 and 1 mg/kg; iv) given 5 min before C17-AP inhibited the secondary hypertensive phase. These results show that C17-AP and C13-AP should be added to the list of compounds capable of releasing EDRF.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide; D010955:Plasmalogens / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
D001095:Arachidonic Acids; D010955:Plasmalogens; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D009569:Nitric Oxide; D000001:Calcimycin; D000255:Adenosine Triphosphate