Increased response to prostaglandin H-2 precedes changes in PGH synthase-1expression in the SHR aorta

AIM: To determine the expression of PGH synthase-1 and the sensitivity of v ascular smooth muscle to PGH(2) in the aorta from the SHR at an age when no endothelium-dependent contractions to acetylcholine are observed under con trol conditions. METHODS: All experiments were performed in parallel on aor tas from 20-wk-old SHR and Wistar-Kyoto normotensive rats (WKY). Rings, wit h or without endothelium, were suspended in conventional organ chambers for the recording of changes in isometric force. The expression of PGH synthas e-1 was evaluated by reverse transcription-polymerase chain reaction (RT-PC R) and Western blot analysis. RESULTS: Under control conditions acetylcholi ne did not cause contractions of rings with or without endothelium. However , in the presence of nitro-L-arginine (NLA, an inhibitor of nitric-oxide sy nthase), it evoked endothelium-dependent contraction in the SHR but not in the WKY aortas. The expression of PGH synthase-1 was comparable in the aort as of both strains (with and without endothelium). PGH2 caused greater cont ractions in rings without endothelium from the SHR than those from WKY, whi le U46,619 evoked a comparable response, in aortas from both strains. CONCL USION: In the aorta of 20-wk-old SHR, endothelium-dependent contractions to acetylcholine are observed only when the production of nitric oxide is pre vented. They are associated with an augmented sensitivity of the smooth mus cle to PGH(2), but not with an increased expression of PGH synthase-1.