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Cardiovascular Research 1999 41(3):682-688; doi:10.1016/S0008-6363(98)00239-9
© 1999 by European Society of Cardiology
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Copyright © 1999, European Society of Cardiology

Altered gene expression of prostacyclin synthase and prostacyclin receptor in the thoracic aorta of spontaneously hypertensive rats

Yasushi Numaguchi*, Mitsunori Harada, Hiroyuki Osanai, Kazunori Hayashi, Yukio Toki, Kenji Okumura, Takayuki Ito and Tetsuo Hayakawa

Internal Medicine II, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan

* Corresponding author. Tel.: +81-52-744-2168; Fax: +81-52-744-2175; E-mail: numa2@tsuru.med.nagoya-u.ac.jp

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.

KEYWORDS Aging; Gene expression; Hypertension; Prostaglandins; Spontaneously hypertensive rat; Wistar–Kyoto rat


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