Key result
Combined treatment with AAA and EET-A prevented hypertension development in young spontaneously hypertensive rats compared to control (systolic blood pressure 134 ± 2 vs 156 ± 5 mmHg; p < 0.05).
Why the study?
Cytochrome P-450-dependent arachidonic acid metabolites regulate blood pressure, vascular tone, and renal function, but the efficiency of combining an EET analog with a 20-HETE antagonist in spontaneously hypertensive rats needed evaluation.
Does the combination of EET-A and AAA prevent hypertension development in spontaneously hypertensive rats?
Does the combination of EET-A and AAA prevent hypertension development in spontaneously hypertensive rats?
Absolute Event Rate: 134% vs 156%
p-value: p=< 0.05
The combination of an EET analog and a 20-HETE antagonist prevents the development of hypertension in young spontaneously hypertensive rats, suggesting a potential novel therapeutic strategy.
Hypothesis-generating for EET-A plus AAA in early hypertension; leaves open translation to human therapy.
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.
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Baranowska et al. (2022) studied Hypertension. EET-A alone or combined with AAA vs. Control group was evaluated on Systolic blood pressure (p=< 0.05). Combined treatment with AAA and EET-A prevented hypertension development in young spontaneously hypertensive rats compared to control (systolic blood pressure 134 ± 2 vs 156 ± 5 mmHg; p < 0.05).
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