25 This study aimed to determine whether prostacyclin (PGI 2 ) functions as an endothelium-26 derived contracting factor (EDCF) in young rat renal arteries, if so, the underlying mechanism(s) 27 and how it alters in pre-hypertensive conditions. Vessels from Wistar-Kyoto (WKY) and pre-28 hypertensive spontaneously hypertensive rats (SHRs) of 25-28 days of age were isolated for 29 functional and biochemical analyses. Result showed that following NO synthase (NOS) 30 inhibition PGI 2 and the

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... oxane-prostanoid (TP) receptor agonist U46619 evoked 31 contractions in young WKY renal arteries that were similar to those in pre-hypertensive SHRs. 32 Meanwhile, the endothelial muscarinic receptor agonist ACh evoked an endothelium-dependent 33 contraction under NOS-inhibited conditions and a production of the PGI 2 metabolite 6-keto-34 PGF 1α ; both were sensitive to cyclooxygenase (COX) and/or COX-1 inhibition, but higher in 35 pre-hypertensive SHRs than in young WKYs. Interestingly, in WKY renal arteries PGI 2 didn't 36 evoke relaxation even after TP receptor antagonism that diminished the contraction evoked by 37 the agonist. Indeed, PGI 2 (IP) receptors were not detected in the vessel with Western blot. 38 Moreover, we noted that treatment with the non-selective COX inhibitor indomethacin, which 39 was started at the pre-hypertensive stage, blunted the elevation of systolic blood pressure and 40 reduced the heart to body ratio in SHR within 2 months of treatment. These results demonstrate 41 that due to scarcity of IP receptors, PGI 2 , which is derived mainly from COX-1-mediated 42 metabolism, acts as an EDCF in young WKY renal arteries and it increases in pre-hypertensive 43 conditions. Also, our data revealed that COX inhibition starting from pre-hypertensive stage has 44 an anti-hypertensive effect in young SHRs. 45