Possible role of prostacyclin synthase in altered prostacyclin generation in DOCA-salt hypertensive rats.
Prostacyclin (PGI2) synthase is one of the key enzymes for vasodepressor PGI2 biosynthesis in the vascular wall. In this study, we attempted to define the alterations in PGI2 synthase and its role in the PGI2 generation in the vascular wall of deoxycorticosterone acetate (DOCA)-salt rats. The PGI2-generating capacity was enhanced significantly when DOCA-salt rats established hypertension, whereas the generation of other arachidonate metabolites, eg, PGE2, PGF2 alpha, and thromboxane, was unaltered. Moreover, the increase in PGI2 generation was associated with an increase in PGI2 synthase activity in the vascular wall. Indeed, the averaged PGI2 generating capacity was closely correlated to the averaged PGI2 synthase activity in DOCA-salt hypertensive rats and three lines of control rats. Incontrast, phospholipase C and phospholipase A2, both of which liberate arachidonate for PGI2 synthesis, were rather lowered in DOCA-salt hypertensive rats. These data clearly indicate that vascular PGI2 generation is increased in the development of DOCA-salt hypertension and that PGI2 synthase is mainly responsible for this enhancement. The increased PGI2 synthase may be relevant to the blood pressure elevation and is expected to have beneficial effects on the vascular protection in hypertension.
2nd Department of Internal Medicine, University of Tokyo, Japan.
Y
Y
Uehara
A
A
Numabe
S
S
Takada
N
N
Hirawa
T
T
Nagata
T
T
Ishimitsu
T
T
Sugimoto
S
S
Yagi
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D003900:Desoxycorticosterone; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000502:physiology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D013931:Thromboxanes; D003900:Desoxycorticosterone; D003577:Cytochrome P-450 Enzyme System; D015237:Dinoprost; D011464:Epoprostenol; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D015232:Dinoprostone