| Title | Antihypertensive effects of selective prostaglandin E-2 receptor subtype 1 targeting |
| Authors | Guan, Youfei Zhang, Yahua Wu, Jing Qi, Zhonghua Yang, Guangrui Dou, Dou Gao, Yuansheng Chen, Lihong Zhang, Xiaoyan Davis, Linda S. Wei, Mingfeng Fan, Xuefeng Carmosino, Monica Hao, Chuanming Imig, John D. Breyer, Richard M. Breyer, Matthew D. |
| Affiliation | Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN USA. Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing, Peoples R China. Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Div Nephrol, 221 Kirkland Hall,S-3223 Med Ctr, Nashville, TN 37232 USA. |
| Keywords | HAMSTER OVARY CELLS PROSTANOID RECEPTORS ANGIOTENSIN-II BLOOD-PRESSURE COLLECTING DUCT PROTEIN-KINASE INDUCED HYPERTENSION KNOCKOUT MICE EP1 RECEPTOR KIDNEY |
| Issue Date | 2007 |
| Publisher | journal of clinical investigation |
| Citation | JOURNAL OF CLINICAL INVESTIGATION.2007,117,(9),2496-2505. |
| Abstract | Clinical use of prostaglandin synthase-inhibiting NSAIDs is associated with the development of hypertension; however, the cardiovascular effects of antagonists for individual prostaglandin receptors remain uncharacterized. The present studies were aimed at elucidating the role of prostaglandin E-2 (PGE(2)) E-prostanoid receptor subtype 1(EP1) in regulating blood pressure. Oral administration of the EP1 receptor antagonist SC51322 reduced blood pressure in spontaneously hypertensive rats. To define whether this antihypertensive effect was caused by EP1 receptor inhibition, an EP1-null mouse was generated using a "hit-and-run" strategy that disrupted the gene encoding EP1 but spared expression of protein kinase N (PKN) encoded at the EP1 locus on the antiparallel DNA strand. Selective genetic disruption of the EP1 receptor blunted the acute pressor response to Ang II and reduced chronic Ang II-driven hypertension. SC51322 blunted the constricting effect of Ang II on in vitro-perfused preglomerular renal arterioles and mesenteric arteriolar rings. Similarly, the pressor response to EP1-selective agonists sulprostone, and 17-phenyltrinor PGE(2) were blunted by SC51322 EP1-null mice. These data support the possibility of targeting the EPI receptor for antihypertensive therapy. |
| URI | http://hdl.handle.net/20.500.11897/397648 |
| ISSN | 0021-9738 |
| DOI | 10.1172/JC129838 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
