Altered gene expression of prostacyclin synthase and prostacyclin receptor in the thoracic aorta of spontaneously hypertensive rats.
OBJECTIVE
The aim of this study was to evaluate the possible role of prostacyclin (PGI2) in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR).


METHODS
Measurement of mRNA and protein levels of PGH synthase (PGHS)-1, PGI2 synthase and the PGI2 receptor, in the thoracic aorta was performed in SHR aged 5, 10, 20, and 40 weeks old and in age-matched normotensive Wistar-Kyoto (WKY) rats with a competitive polymerase chain reaction method and immunoblotting. Aortic production of 6-keto-PGF1 alpha, the main metabolite of PGI2, was also measured.


RESULTS
Compared with age-matched WKY rats, PGHS-1 mRNA and protein levels in the thoracic aorta of SHR increased with age, reaching three- and twofold higher than WKY rats at 40 weeks old, respectively. PGI2 synthase mRNA and protein levels in SHR were significantly higher than in WKY rats at 20 and 40 weeks old. In contrast, PGI2 receptor mRNA levels in SHR were consistently lower than in WKY rats at all ages.


CONCLUSIONS
These results provide evidence that hypertension elicits alterations in levels of arachidonic acid metabolites, including PGH2 and PGI2. They also suggest that the decreased expression of PGI2 receptor mRNA in prehypertensive SHR could be one of the causes of hypertension in SHR.
Numaguchi
Y
Y
Internal Medicine II, Nagoya University School of Medicine, Japan. numa2@tsuru.med.nagoya-u.ac.jp
Harada
M
M
Osanai
H
H
Hayashi
K
K
Toki
Y
Y
Okumura
K
K
Ito
T
T
Hayakawa
T
T
D000375:Aging / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression; D006973:Hypertension / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000032:analysis / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D003577:Cytochrome P-450 Enzyme System; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase