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Fenofibrate prevents the development of angiotensin II-dependent hypertension in mice
Trinity Vera1, Montoya Taylor, Quinn Bohman
1Department of Physiology & Biophysics, for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Abstract:
Previous studies have indicated that the production of 20-hydroxyecisatatraenoic acid (20-HETE) is similar in the liver of C57/B6 mice and rats, but the renal production of 20-HETE is very low in this strain of mice. The present study examined the effects of induction of the renal production of 20-HETE with fenofibrate (FF) on the development of angiotensin II (Ang II)-dependent hypertension in C57BL/6J mice. The mice were divided into 4 groups and treated with vehicle (control), FF (90 mg/kg per day, IP), Ang II (1000 ng/kg per minute, SC), and Ang II plus FF. Mean arterial blood pressure (MAP) averaged 109+/-4 and 106+/-2 mm Hg in control and FF-treated mice (n=7). MAP was significantly increased in the Ang II-treated mice to 144+/-4 mm Hg (n=7). However, FF treatment prevented the development of Ang II-dependent hypertension, with MAP averaging 115+/-5 mm Hg in mice treated with both Ang II plus FF (n=7). Renal production of 20-HETE was very low in control (n=7) and Ang II-treated (n=7) mice and was increased by >2-fold in FF-treated (n=7) and Ang II plus FF-treated (n=7) mice. The levels of Cyp4A proteins were markedly increased in the kidneys of mice treated with FF and Ang II plus FF but not in the renal vasculature. These results suggest that upregulation of the production of 20-HETE in renal tubules may contribute to the blood pressure-lowering effects of FF treatment in Ang II-dependent hypertension in C57BL/6J mice.
Insights
Fenofibrate increases renal 20-HETE production, preventing angiotensin II-induced hypertension in mice. This suggests targeting 20-hydroxyecisatatraenoic acid (20-HETE) may treat high blood pressure.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Research
Background:
- Renal 20-hydroxyecisatatraenoic acid (20-HETE) production is low in C57BL/6J mice.
- Angiotensin II (Ang II) is known to induce hypertension.
Purpose of the Study:
- To investigate the effect of fenofibrate (FF) on angiotensin II-dependent hypertension in mice.
- To determine if inducing renal 20-HETE production can mitigate hypertension.
Main Methods:
- C57BL/6J mice were divided into four groups: control, FF, Ang II, and Ang II plus FF.
- Mean arterial blood pressure (MAP) was measured.
- Renal 20-HETE and Cyp4A protein levels were analyzed.
Main Results:
- Fenofibrate alone did not affect blood pressure.
- Ang II significantly increased MAP, inducing hypertension.
- Fenofibrate treatment prevented Ang II-induced hypertension, maintaining MAP near control levels.
- Fenofibrate increased renal 20-HETE production and Cyp4A protein levels, particularly in renal tubules.
Conclusions:
- Upregulation of renal 20-HETE production by fenofibrate may lower blood pressure.
- Targeting renal 20-HETE synthesis could be a therapeutic strategy for Ang II-dependent hypertension.
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