Redox regulation and NO/cGMP plus K+ channel activation contributes to cardiorenal protection induced by Cuphea carthagenensis (Jacq.) J.F. Macbr. in ovariectomized hypertensive rats.
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BACKGROUND
One of the medicinal plants widely used by the population in the treatment of hypertension, atherosclerosis and circulatory disorders is Cuphea carthagenensis (Jacq.) J.F. Macbr. (Lythraceae), popularly known as 'sete sangrias', being found in Brazil, Hawaii and in South Pacific Islands. Despite the widespread use of this species by the population, its long-term antihypertensive and cardioprotective activities have not yet been scientifically evaluated.
OBJECTIVE
To evaluate the possible cardioprotective effects of an ethanol-soluble fraction obtained from C. carthagenensis (ESCC) using ovariectomized hypertensive rats to simulate a broad part of the female population over 50 years of age affected by hypertension. In addition, the molecular mechanism that may be responsible for its cardiorenal protective effects was also explored.
METHODS
Female Wistar rats were submitted to surgical procedures of bilateral ovariectomy and induction of renovascular hypertension (two-kidneys, one-clip model). The sham-operated group was used as negative control. ESCC was obtained and a detailed phytochemical investigation about its main secondary metabolites was performed. ESCC was orally administered at doses of 30, 100 and 300 mg/kg, daily, for 28 days, 5 weeks after surgery. Enalapril (15 mg/kg) was used as standard antihypertensive drug. Renal function was evaluated on days 1, 7, 14, 21 and 28. At the end of the experimental period, systolic, diastolic, mean arterial pressure and heart rate were recorded. The activity of the tissue enzymatic antioxidant system, thiobarbituric acid reactive substances, nitrotyrosine, nitrite, aldosterone and vasopressin levels, in addition to the activity of the angiotensin-converting enzyme were also evaluated. Additionally, vascular reactivity to acetylcholine, sodium nitroprusside, and phenylephrine, and the role of nitric oxide, prostaglandins, and K+ channels in the vasodilator response of ESCC on the mesenteric vascular bed were also investigated.
RESULTS
ESCC-treatment induced an important cardiorenal protective response, preserving renal function and preventing elevation of blood pressure and heart rate in ovariectomized hypertensive rats. In addition, prolonged treatment with ESCC recovered mesenteric vascular reactivity at all doses used. This effect was associated with an important modulation of the antioxidant defense system with a possible increase in NO bioavailability. Additionally, NO/cGMP activation and K+ channel opening-dependent vasodilator effect was observed on the mesenteric vascular bed, indicating a potential mechanism for the cardiovascular effects of ESCC.
CONCLUSIONS
A 28-days ESCC treatment reduces the progression of the cardiorenal disease in ovariectomized hypertensive rats. These effects seem to be involved with an attenuation of oxidative and nitrosative stress, affecting endothelial nitric oxide production and K+ channel opening in smooth muscle cells.
