title: A vasoconstrictor response to COX-1-mediated prostacyclin synthesis in young rat renal arteries that increases in prehypertensive conditions.
abstract: This study aimed to determine whether prostacyclin (PGI2) functions as an endothelium-derived contracting factor (EDCF) in young rat renal arteries, and, if so, we wanted to examine the underlying mechanism(s) and how it changes in prehypertensive conditions. Vessels from Wistar-Kyoto (WKY) and prehypertensive spontaneously hypertensive rats (SHRs) of 25-28 days of age were isolated for functional and biochemical analyses. Result showed that following NO synthase (NOS) inhibition PGI2 and the thromboxane-prostanoid (TP) receptor agonist U-46619 evoked contractions in young WKY renal arteries that were similar to those in prehypertensive SHRs. Meanwhile, the endothelial muscarinic receptor agonist ACh evoked an endothelium-dependent contraction under NOS-inhibited conditions and a production of the PGI2 metabolite 6-keto-PGF1α; both were sensitive to cyclooxygenase (COX) and/or COX-1 inhibition but higher in prehypertensive SHRs than in young WKYs. Interestingly, in WKY renal arteries PGI2 did not evoke relaxation even after TP receptor antagonism that diminished the contraction evoked by the agonist. Indeed, PGI2 (IP) receptors were not detected in the vessel with Western blot. Moreover, we noted that treatment with the nonselective COX inhibitor indomethacin, which was started at the prehypertensive stage, blunted the elevation of systolic blood pressure and reduced the heart-to-body ratio in SHR within 2 mo of treatment. These results demonstrate that due to scarcity of IP receptors, PGI2, which is derived mainly from COX-1-mediated metabolism, acts as an EDCF in young WKY renal arteries, and it increases in prehypertensive conditions. Also, our data revealed that COX inhibition starting from the prehypertensive stage has an antihypertensive effect in young SHRs.
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China; and.
authors.forename: Dongling
authors.initials: D
authors.lastname: Liu
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China; and.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: The Central Lab, Shantou University Medical College, Shantou, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Luo
authors.affiliation: The Central Lab, Shantou University Medical College, Shantou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China; and.
authors.forename: Yingzhan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China; and yz_sumc@163.com.
authors.forename: Yingbi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000819:agonists; D012077:Renal Artery / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D014661:Vasoconstriction
chemical_list: D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D018721:Muscarinic Agonists; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat
keywords: contraction; prostacyclin; prostacyclin receptors; thromboxane-prostanoid receptors