Enhanced formation of PGI2, a potent hypotensive substance, by aortic rings and homogenates of the spontaneously hypertensive rat.
Intact rings and homogenates of aorta from spontaneously hypertensive rats (SHR) contain enhanced capacity over normal rats (NR) to convert arachidonic acid into PGI2. The PGI2 synthetic system in SHR is stimulated to a greater extent than NR by norepinephrine. Indomethacin blocks this stimulation. PGE2 and PGF2alpha were detected in much smaller amounts in homogenates (undetected in rings) but their formation was not enhanced by the hypertensive tissue. The identity of PGI2 was based on 1) direct pharmacological assay on the rat blood pressure. In this system identical vasodepressor responses to PGI2 are observed after intracarotid and intrajugular administration 2) indirectly as 6-keto PGF1alpha isolated after incubation of aortic homogenates with tritiated arachidonic acid and 3) indirectly by GC-MS assay of PGE2, PGF2alpha and 6-keto PGF1alpha formed during incubation of aortic homogenates with excess unlabeled arachidonic acid. These results provide additional support to our recent hypothesis that PGI2, of aortic origin, might actively participate in the regulation of systemic blood pressure. Its enhanced formation by intact hypertensive vascular tissue reflects an increase in the number of enzyme molecules immediately available to the substrate. This could probably be an adaptive response to the elevated levels of catecholamines in the circulation.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002849:Chromatography, Gas; D011464:Epoprostenol / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D013058:Mass Spectrometry; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D051381:Rats; D013997:Time Factors
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D011464:Epoprostenol; D007213:Indomethacin