MOLECULAR PHYSIOLOGICAL MECHANISM OF AGERELATED CHANGES IN PRODUCTION OF NITRIC OXIDE AND PGI2

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We demonstrated that several vasoconstricting peptides such as angiotensin II (AII) and endothelin-1 (ET-1) increased the production of nitric oxide (NO) and prostacyclin (PGI_2) in the rat hearts. Aging modulated the endothelial function to change the production of NO and PGI_2. It is implicated that PGI_2 plays an important role in the pathogenesis of hypertension, atherosclerosis and thrombosis due to its vasodilating and anti-platelet effect. We examined the age-related changes in the expression of enzymes responsible for the synthesis of PGI_2 and of PGI_2 receptors to reveal the mechanism of regulation of PGI_2 production. Aorta and hearts were isolated from 3-, and 27-months old Fischer 344 rats. Hearts were perfused with constant pressure (75 cmH_2O) at 37℃. Changes in the coronary flow were measured with a flow meter. 6-keto-PGF_1a in the coronary effluent was measured with EIA.Changes in the expression of PGI_2 receptors, PGI synthase and cyclooxygenase-1 (COX-1) were quantified by real-time PCR and Western blot analysis. Release of PGI_2 into the effluent was greater in the aged rat than young rat. There was no age-related difference in the amount of PGI_2 receptor. Expression of COX-1 and PGI synthase was increased in the aged rat. These increases in COX-1 and PGI synthase may be responsible for the increased production of PGI_2 in the aged rat coronary artery.