Cited by 195Renin-Angiotensin System StudiesEicosanoids and Hypertension PharmacologyNitric Oxide and Endothelin Effects

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A Mouse Model of Angiotensin II Slow Pressor Response: Role of Oxidative Stress

Kawada, Noritaka, Imai, Enyu, Karber, Alexsander, Welch, William J., Wilcox, Christopher S.·2002·Journal of the American Society of Nephrology

DOI 10.1097/01.asn.0000035087.11758.ed

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Abstract

ABSTRACT. The slow pressor response to prolonged infusions of angiotensin II (AngII) entails a delayed rise in BP. This study investigated the hypothesis that the response depends on the generation of oxidative stress. The BP and renal functional response of mice to graded doses (200, 400, and 1000 ng. kg(-1). min(-1)) of subcutaneously infused AngII was studied. The SBP of conscious mice increased by day 3 at AngII1000 but showed a delayed rise by days 9 to 13 (slow pressor response) at the lower rates of AngII infusion. By day 13, there was a graded increase in SBP with the rate of AngII infusion (Vehicle, -2.6 +/- 2.6%; AngII200, +14.1 +/- 5.0%; AngII400, +31.9 +/- 1.9%; AngII1000, +43.2 +/- 5.5%). The MAP measured under anesthesia rose significantly (P < 0.001) with AngII400 at 14 d (Vehicle, 85 +/- 2 mmHg; AngII400, 100 +/- 3 mmHg). When studied at day 6, the MAP of AngII400 rats was not elevated (88 +/- 2 mmHg; NS versus vehicle), yet the GFR was higher (1.05 +/- 0.05 versus 1.25 +/- 0.05 ml. min(-1). g(-1); P < 0.05) accompanied by an increase in the filtration fraction (FF) (28.8 +/- 1.2 versus 37.2 +/- 0.8%; P < 0.001). From day 6 through day 14, the MAP had increased (P < 0.01) in AngII400, accompanied by a significant reduction in GFR to 1.05 +/- 0.04 ml. min(-1). g(-1) (P < 0.01) and elevation of renal vascular resistance (RVR) (day 6 versus day 14, 15.3 +/- 0.6 versus 19.2 +/- 1.2 mmHg. ml(-1). min(-1). g(-1); P < 0.05). Renal excretion of 8-iso PGF(2alpha) was increased in AngII400 group at day 12 (2.52 +/- 0.35 versus 5.85 +/- 0.78 pg. day(-1); P < 0.01). The permeant superoxide dismutase mimetic tempol reduced the effects of AngII400 on the SBP (-1.7 +/- 5.8%; P < 0.01), the MAP (87 +/- 4 mmHg; P < 0.01), and the RVR (15.2 +/- 0.5 mmHg. ml(-1). min(-1). g(-1); P < 0.05) at day 14 and the renal 8-iso PGF(2alpha) excretion (3.53 +/- 0.71 pg. d(-1); P < 0.05) at day 12. It is concluded that the AngII infused mouse is a valid model for the slow pressor response. There is an early rise in GFR and FF, consistent with increased postglomerular vascular resistance and a late rise in RVR with a fall in GFR, consistent with increased preglomerular vascular resistance that is accompanied by a rise in BP. There is evidence of increased oxidative stress that is implicated in the increase in the BP and RVR in this model.

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Authors: Kawada, N., Imai, E., Karber, A., Welch, W. J., & Wilcox, C. S.
Affiliations: Georgetown University (US)
The University of Osaka (JP)
Corresponding author: Kawada, Noritaka
Welch, William J.
Wilcox, Christopher S.
ORCID: Imai, Enyu
Welch, William J.
Wilcox, Christopher S.
Venue: Journal of the American Society of Nephrology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2002-12
Volume: 13
Issue: 12
Pages: 2860-2868
ISSN: 1046-6673 (ISSN-L)
DOI: 10.1097/01.asn.0000035087.11758.ed
OpenAlex: W2127905773
Cited by: 195
References: 47
Citations by year: 2026: 3 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 7 · 2016: 11 · 2015: 8 · 2014: 8 · 2013: 7 · 2012: 9
FWCI: 7.46
Type: journal article
Language: en
Open access: closed
Locations: Journal of the American Society of Nephrology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Heart, Lung, and Blood Institute (HL‐68686, P01HL068686)
National Institute of Diabetes and Digestive and Kidney Diseases (DK‐49870, DK 36079, R01DK049870)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: angiotensin II, oxidative stress, blood pressure, renal function, glomerular filtration rate, filtration fraction, renal vascular resistance, renal excretion, rats, infusion rate, renal hemodynamics, nitric oxide synthase inhibition, angiotensin II receptor, renin-angiotensin system
MeSH terms: Angiotensin II, Animals, Antioxidants, Blood Pressure, Cyclic N-Oxides, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Combinations, Infusion Pumps, Kidney, Male, Mice, Inbred C57BL, Spin Labels, Systole, Vasoconstrictor Agents, Dinoprost, Oxidative Stress, F2-Isoprostanes, Mice

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A Mouse Model of Angiotensin II Slow Pressor Response: Role of Oxidative Stress

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