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

Abstract

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-PGF_1α, 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.