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Cyclooxygenase (COX)‐1 derived prostaglandin E2 (PGE2) acting on its type 1 receptor (EP1R) mediates slow‐pressor angiotensin‐II (AngII) hypertension
Author(s) -
Peterson Jeffrey,
Burmeister Melissa A,
Marden Jennifer,
Poor Daniel,
Nwakeze Chiamaka,
Sharma Ram V,
Anrather Josef,
Iadecola Costantino,
Davisson Robin L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.802.2
Subject(s) - angiotensin ii , cyclooxygenase , medicine , endocrinology , prostaglandin , prostaglandin e2 , prostaglandin e , renin–angiotensin system , receptor , mean arterial pressure , blood pressure , chemistry , enzyme , heart rate , biochemistry
COX‐derived prostaglandins have long been implicated in the cardiovascular effects of AngII. Recently a role for PGE 2 acting on EP 1 R, has emerged in AngII‐dependent vasopressor effects. However, the role of this pathway in slow‐pressor AngII hypertension has not been investigated. Here we hypothesized that slowly developing AngII hypertension is mediated by PGE 2 acting on EP 1 R. We also explored the enzymatic source of PGE 2 involved. COX‐1, COX‐2 or EP 1 R null mice and wildtype (WT) controls were implanted with telemeters for mean arterial pressure (MAP) recordings during slow‐pressor AngII infusion (600ng/kg/min, 2 wks). Baseline MAP was similar between groups (WT 95±2, n=7; COX‐1 −/− 93±2, n=5; COX‐2 −/− 96±7, n=4; EP 1 R −/− 100±2 mmHg, n=4, p>.05). In WT mice, AngII induced the typical slow rise in MAP that peaked during the second week of infusion (ΔMAP 32±6, p<.05). This response was completely prevented in EP 1 R −/− mice (ΔMAP 2±4, p<.05). The hypertension was also blocked in COX‐1 −/− mice (ΔMAP 5±1, p<.05), whereas the rise in MAP was intact in COX‐2 −/− mice (ΔMAP 34±4, p>.05). Furthermore, power spectral analysis revealed a significant increase in sympathetic activation in WT mice that was absent in EP 1 R −/− (LF/HF WT 2.2±.4, n=3; EP 1 R −/− 0.7±.3 fold baseline, n=4, p<.05). These results demonstrate that COX‐1‐derived PGE 2 acting on EP 1 R is critical in AngII slow‐pressor hypertension, and suggest that this pathway is required for the accompanying AngII induced sympathetic activation in this model of hypertension. Supported by HL063887, HL084624, AHA 0540114N.