title: Inhibition of renin release by arachidonic acid metabolites, 12(s)-HPETE and 12-HETE: role of TRPV1 channels.
abstract: We test the hypothesis that 12-hydroperoxyeicosatetraenoic acid (12(s)-HPETE) and 12-hydroxyeicosatetraenoic acid (12-HETE) perfused into the renal pelvis increase afferent renal nerve activity (ARNA) and suppress renin release in rats fed a low-salt (LS) diet via activation of the transient receptor potential vanilloid type 1 (TRPV1) expressed in renal sensory nerves. 12(s)-HPETE or 12-HETE given into the left renal pelvis dose-dependently increased ARNA, which was abolished by AMG9810, a selective TRPV1 antagonist, or by RP67580, a selective neurokinin 1 receptor antagonist, in normal salt or LS-treated rats. 12(s)-HPETE, 12-HETE, or substance P perfused into the left renal pelvis suppressed plasma angiotensin I (Ang I) levels in LS rats, which was abolished by AMG9810 or attenuated by ipsilateral renal denervation (RD). 12(s)-HPETE or 12-HETE increased release of substance P and calcitonin gene-related peptide from the ipsilateral kidney, which was abolished by AMG9810 but not RP67580, RD, or RP67580 plus RD. Immunofluorescence staining showed that TRPV1-positive nerve fibers located in the renal cortex, medulla, and pelvis, and that the sympathetic nerve marker, neuropeptide Y, but not neurokinin 1 receptors expressed in the juxtaglomerular region colocalized with renin. Thus, our data show that 12(s)-HPETE and 12-HETE enhance ARNA and substance P/calcitonin gene-related peptide release but suppress renin activity in LS rats, and these effects are abolished when TRPV1 is blocked. These results indicate that TRPV1 mediates 12(s)-HPETE and 12-HETE action in the kidney in such a way that dysfunction in TRPV1 may lead to disintegrated regulation of renin and renal function.
authors.affiliation: Department of Medicine, the Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Chaoqin
authors.initials: C
authors.lastname: Xie
authors.forename: Donna H
authors.initials: DH
authors.lastname: Wang
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000494:pharmacology*; D000803:Angiotensin I / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D015289:Leukotrienes / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000032:analysis; D012083:Renin / Q000032:analysis / Q000378:metabolism; D050916:TRPV Cation Channels / Q000032:analysis / Q000502:physiology*; D000092502:Renin Inhibitors
chemical_list: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000803:Angiotensin I; D016718:Arachidonic Acid; D015289:Leukotrienes; D018040:Receptors, Neurokinin-1; D012083:Renin; D050916:TRPV Cation Channels; D000092502:Renin Inhibitors; C493922:Trpv1 protein, rat; C021201:12-HPETE