Antihypertensive effect of myricetin in combination with ramipril, an angiotensin-1-converting enzyme inhibitor: involvement of critical enzymes in blood pressure regulation

Hypertension, a state where systolic blood pressure is 140 mmHg or higher and/or diastolic blood pressure is 90 mmHg or higher, plays a critical role in the development of serious cardiovascular conditions. It is a major cause of morbidity and mortality worldwide, affecting over one billion adults. This study investigated the effect of myricetin (a flavanol found in fruits and vegetables) in combination with ramipril on the blood pressure regulation, critical enzyme activities, nitric oxide level. It also evaluated the effect on inflammatory parameters, as well as gene expression relevant to hypertension in rats. The rats were divided into nine groups of eight rats each and treated as follows: Control rats were given normal saline (0.9% NaCl), rats received oral daily dose of L-NAME (hypertensive rats), rats administered 25 mg/kg/day of myricetin, rats administered 50 mg/kg/day of myricetin, rats administered ramipril 2 mg/kg/day, hypertensive rats administered 25 mg/kg/day of myricetin, hypertensive rats administered 50 mg/kg/day of myricetin, hypertensive rats administered 2 mg/kg/day of ramipril, and hypertensive rats coadministered 50 mg/kg/day myricetin and 2 mg/kg/day of ramipril for 14 consecutive days. Thereafter, the changes in blood pressure were carried out at intervals during the experiment; then, some critical enzymes relevant to hypertension were evaluated. L-NAME-treated rats showed increased blood pressure (systolic and diastolic) and elevated activities of angiotensin-1-converting enzymes (ACE), arginase, and acetylcholinesterase (AChE), with a concomitant decrease in levels of nitric oxide (NO) when compared with control. However, combination of myricetin and ramipril reduced the blood pressure and inhibited ACE, AChE, arginase activities when compared to control. In addition, combined treatment significantly upregulated ACE mRNA expression, downregulated eNOS gene expression, and increased levels of NO compared with hypertensive-treated rats. This finding supports the concept that the combination strategy might be an alternative therapy in the management/prevention of hypertension.