title: TP receptors regulate renal hemodynamics during angiotensin II slow pressor response.
abstract: We investigated the hypothesis that thromboxane A2 (TxA2)-prostaglandin H2 receptors (TP-Rs) mediate the hemodynamic responses and increase in reactive oxygen species (ROS) to ANG II (400 ng x kg(-1) x min(-1) sc for 14 days) using TP-R knockout (TP -/-) and wild-type (+/+) mice. TP -/- had normal basal mean arterial blood pressure (MAP) and glomerular filtration rate but reduced renal blood flow and increased filtration fraction (FF) and renal vascular resistance (RVR) and markers of ROS (thiobarbituric acid-reactive substances and 8-isoprostane PGF2alpha) and nitric oxide (NOx). Infusion of ANG II into TP +/+ increased ROS and thromboxane B2 (TxB2) and increased RVR and FF. ANG II infusion into TP -/- mice reduced ANG I and increased aldosterone but caused a blunted increase in MAP (TP -/- : +6 +/- 2 vs. TP +/+: +15 +/- 3 mmHg) and failed to increase FF, ROS, or TxB2 but increased NOx and paradoxically decreased RVR (-2.1 +/- 1.7 vs. +2.6 +/- 0.8 mmHg x ml(-1) x min(-1) x g(-1)). Blockade of AT1 receptor of TP -/- mice infused with ANG II reduced MAP (-8 mmHg) and aldosterone but did not change the RVR or ROS. In conclusion, during an ANG II slow pressor response, AT1 receptors activate TP-Rs that generate ROS and prostaglandins but inhibit NO. TP-Rs mediate all of the increase in RVR and FF, part of the increase in MAP, but are not implicated in the suppression of ANG I or increase in aldosterone. TP -/- mice have a basal increase in RVR and FF associated with ROS.
authors.affiliation: Cardiovascular Kidney Institute and Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007, USA.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kawada
authors.forename: Kathryn
authors.initials: K
authors.lastname: Dennehy
authors.forename: Glenn
authors.initials: G
authors.lastname: Solis
authors.forename: Paul
authors.initials: P
authors.lastname: Modlinger
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hamel
authors.forename: Julie T
authors.initials: JT
authors.lastname: Kawada
authors.forename: Shakil
authors.initials: S
authors.lastname: Aslam
authors.forename: Toshiki
authors.initials: T
authors.lastname: Moriyama
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.forename: William J
authors.initials: WJ
authors.lastname: Welch
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000450:Aldosterone / Q000652:urine; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001835:Body Weight; D015237:Dinoprost / Q000652:urine; D004573:Electrolytes / Q000097:blood; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006339:Heart Rate; D006400:Hematocrit; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000033:anatomy & histology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D009929:Organ Size; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013929:Thromboxane B2 / Q000652:urine; D014556:Urine; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004573:Electrolytes; D009566:Nitrates; D009573:Nitrites; D044140:Receptor, Angiotensin, Type 1; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D017392:Thiobarbituric Acid Reactive Substances; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000450:Aldosterone; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000803:Angiotensin I; D015237:Dinoprost; D011464:Epoprostenol