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Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L‐NG‐nitro arginine methyl ester (L‐NAME), an analog of L‐arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L‐NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L‐NAME‐induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L‐NAME‐induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin‐converting enzyme (ACE) and endothelin‐1. Moreover, they exhibit anti‐inflammatory effects, attenuating inflammation‐mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L‐NAME‐induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.
Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L‐NG‐nitro arginine methyl ester (L‐NAME), an analog of L‐arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L‐NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L‐NAME‐induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L‐NAME‐induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin‐converting enzyme (ACE) and endothelin‐1. Moreover, they exhibit anti‐inflammatory effects, attenuating inflammation‐mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L‐NAME‐induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.
Background: Ang II plays important roles in controlling stability of BP. ERAP1 can regulate BP by reducing the level of Ang II. However, the downstream mechanisms of activated Ang II which are activated by ERAP1 deletion have not been identified. Methods: Tail-cuff was used to measure BP in the ERAP1 deficient and wt mice. Ang II were evaluated by LC-MS. Aldo were measured with ELISA kits. PAH clearance was collected and used to calculate renal plasma flow (RPF) . RT-qPCR, immunochemistry staining, and bulk RNA sequencing were applied to identify the mechanisms. Two medications (Enalapril and Amlodipine) were used as control. BP data was collected to examine the influence of ERAP1 rs30187 risk allele carriers to SSBP. Results: Ang II were upregulated and induced hypertension in ERAP1 deficient mice. BP did not show sex differences, while Ang II expression exhibited sex dimorphism. Along with an increase of Aldo levels, the expressions of ERAP1 and CYP11B2 were co-knockdown in ZG cells in male ERAP1+/- mice. Different activated genes were further detected. While in ERAP1+/- females, decreased RPF and lower ERAP1 and CD31 expressions in endothelial cells were observed. Enalapril took effects in dropping BP and decreasing Aldo production. Smaller BP decline and no difference of RPF in females was confirmed in Amlodipine group. People <51 years old with the ERAP1 rs30187 risk allele exhibited increased SSBP. Conclusions: ERAP1 exerted BP control by regulating Ang II. In male ERAP1+/- mice, the primary regulated mechanism occurred in adrenals, where overexpressed Ang II targeted ZG cells, activated Aldo production pathway. In female ERAP1+/- mice, the prominent mechanism was dependent on the alterations of vascular, elevated Ang II downregulated endothelial cells' proliferation, decreased RPF and exacerbated renal vascular function. Enalapril had stronger effects in regulating RAAS and Amlodipine played important roles in relaxing the vessels.
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