TY - JOUR
T1 - Epoxyeicosatrienoic Acid Analog and 20-HETE Antagonist Combination Prevent Hypertension Development in Spontaneously Hypertensive Rats
AU - Baranowska, Iwona
AU - Gawrys, Olga
AU - Walkowska, Agnieszka
AU - Olszynski, Krzysztof H.
AU - Červenka, Luděk
AU - Falck, John R.
AU - Adebesin, Adeniyi M.
AU - Imig, John D.
AU - Kompanowska-Jezierska, Elżbieta
N1 - Funding Information:
This study was supported by the National Science Centre (project number 2017/26/M/NZ5/00367). The Robert A. Welch Foundation provided support to JF (I-0011). A Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A., Trustee Grant was awarded to JF and JI. JF and JI have patents that cover the composition of matter for EET-A and AAA.
Publisher Copyright:
Copyright © 2022 Baranowska, Gawrys, Walkowska, Olszynski, Červenka, Falck, Adebesin, Imig and Kompanowska-Jezierska.
PY - 2022/1/17
Y1 - 2022/1/17
N2 - Numerous studies indicate a significant role for cytochrome P-450-dependent arachidonic acid metabolites in blood pressure regulation, vascular tone, and control of renal function. Epoxyeicosatrienoic acids (EETs) exhibit a spectrum of beneficial effects, such as vasodilatory activity and anti-inflammatory, anti-fibrotic, and anti-apoptotic properties. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that inhibits sodium reabsorption in the kidney. In the present study, the efficiency of EET-A (a stable analog of 14,15-EET) alone and combined with AAA, a novel receptor antagonist of 20-HETE, was tested in spontaneously hypertensive rats (SHR). Adult SHR (16 weeks old) were treated with two doses of EET-A (10 or 40 mg/kg/day). In the following experiments, we also tested selected substances in the prevention of hypertension development in young SHR (6 weeks old). Young rats were treated with EET-A or the combination of EET-A and AAA (both at 10 mg/kg/day). The substances were administered in drinking water for 4 weeks. Blood pressure was measured by telemetry. Once-a-week observation in metabolic cages was performed; urine, blood, and tissue samples were collected for further analysis. The combined treatment with AAA + EET-A exhibited antihypertensive efficiency in young SHR, which remained normotensive until the end of the observation in comparison to a control group (systolic blood pressure, 134 ± 2 versus 156 ± 5 mmHg, respectively; p < 0.05). Moreover the combined treatment also increased the nitric oxide metabolite excretion. Considering the beneficial impact of the combined treatment with EET-A and AAA in young rats and our previous positive results in adult SHR, we suggest that it is a promising therapeutic strategy not only for the treatment but also for the prevention of hypertension.
AB - Numerous studies indicate a significant role for cytochrome P-450-dependent arachidonic acid metabolites in blood pressure regulation, vascular tone, and control of renal function. Epoxyeicosatrienoic acids (EETs) exhibit a spectrum of beneficial effects, such as vasodilatory activity and anti-inflammatory, anti-fibrotic, and anti-apoptotic properties. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that inhibits sodium reabsorption in the kidney. In the present study, the efficiency of EET-A (a stable analog of 14,15-EET) alone and combined with AAA, a novel receptor antagonist of 20-HETE, was tested in spontaneously hypertensive rats (SHR). Adult SHR (16 weeks old) were treated with two doses of EET-A (10 or 40 mg/kg/day). In the following experiments, we also tested selected substances in the prevention of hypertension development in young SHR (6 weeks old). Young rats were treated with EET-A or the combination of EET-A and AAA (both at 10 mg/kg/day). The substances were administered in drinking water for 4 weeks. Blood pressure was measured by telemetry. Once-a-week observation in metabolic cages was performed; urine, blood, and tissue samples were collected for further analysis. The combined treatment with AAA + EET-A exhibited antihypertensive efficiency in young SHR, which remained normotensive until the end of the observation in comparison to a control group (systolic blood pressure, 134 ± 2 versus 156 ± 5 mmHg, respectively; p < 0.05). Moreover the combined treatment also increased the nitric oxide metabolite excretion. Considering the beneficial impact of the combined treatment with EET-A and AAA in young rats and our previous positive results in adult SHR, we suggest that it is a promising therapeutic strategy not only for the treatment but also for the prevention of hypertension.
KW - 20-HETE antagonist
KW - EET analog
KW - epoxyeicosatrienoic acids
KW - primary hypertension
KW - spontaneously hypertensive rats
UR - http://www.scopus.com/inward/record.url?scp=85123754260&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123754260&partnerID=8YFLogxK
U2 - 10.3389/fphar.2021.798642
DO - 10.3389/fphar.2021.798642
M3 - Article
C2 - 35111064
AN - SCOPUS:85123754260
SN - 1663-9812
VL - 12
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 798642
ER -