Abstract
Purpose: To evaluate the hypotensive, vasorelaxant and antihypertensive effects elicited by the hydroalcohol extract from the fruits of Syzygium cumini (EHSCF) in non-anesthetized rats. Methods: The rats were anesthetized and polyethylene catheters were inserted into the lower abdominal aorta and into the inferior vena cava for blood pressure measurements and administration of drugs. After a recovery period of 24 h, EHSCF (0.5; 1; 5; 10; 20 and 30 mg/kg, i.v.) was administered in non-anesthetized rats. The mean arterial pressure and the heart rate were recorded. To investigate the effects of extract, doses EHSCF were administered after pretreatment with L-NAME, atropine, indomethacin, and hexamethonium. For measurement of isometric tension, a concentration-response curve was obtained after Phenylephrine and KCl (80 mM) pre-contractions. The bioactive extract was analyzed via mass spectrometry (MS) fingerprinting using direct electrospray ionization mass spectrometry (ESI-MS). Results: EHSCF (0.5; 1; 5; 10; 20 and 30 mg/kg) induced hypotension (-15 ± 1, -14 ± 1, -15 ± 1, -13 ± 1, -11 ± 1 and -13 ± 2 %) and bradycardia (-6 ± 1, -5 ± 1, -6 ± 1, -14 ± 1, -8 ± 1 and -10 ± 2 %) in normotensive rats. These responses were attenuated by pre-treatment with L-NAME, indomethacin, hexamethonium or atropine. In phenylephrine, pre-contracted mesenteric rings, EHSCF-induced relaxation (Emax = 54.6 ± 4.5 % and pD2 = 2.7 ± 0.1) that were affected by endothelium removal. EHSCF caused relaxant effect of KCl (80 mM) pre-contracted rings (Emax = 100 ± 0.2 % and pD2 = 2.2 ± 0.1). This effect was not changed in denuded rings. A single oral administration of the extract reduced significant mean arterial pressure in spontaneously hypertensive rats. ESI-MS/MS analyses of EHSCF demonstrated that the major constituents of the analyzed samples coincided with the mass of the malic, gallic, caffeic and ferulic acids. Conclusion: The results suggest that EHSCF induces hypotension probably due to a decrease in peripheral resistance, mediated by the endothelium. Bradycardia may be due to indirect cardiac muscarinic activation. The extract also causes an antihypertensive effect.
Highlights
The hypertension is the most common cardiovascular disease and is a major public health issue, affecting more than 10 % of the worldwide population [1]
The ESI-mass spectrometry (MS) fingerprints technique was used to characterize the presence of bioactive compounds in theses edible fruits
These analyses showed that the detected constituents in EHSCF were coincided with the mass of the phenolic acids such as: malic, gallic, caffeic and ferulic acids (Table 1, Figure 1)
Summary
The hypertension is the most common cardiovascular disease and is a major public health issue, affecting more than 10 % of the worldwide population [1]. For example: The aqueous extract of leaves produced hypotensive effects in anesthetized normotensive rats [6]. We examined the effects of the hydroalcoholic extract of the fruits of S. cumini (EHSCF) on blood pressure and vascular tone in non-anesthetized rats, using in vitro and in vivo approaches. Using AQCAD software (AVS Projects, SP, Brazil), data were sampled every 500 Hz. The computer calculated mean arterial pressure (MAP) and heart rate (HR). We studied the concentration-dependent relaxant effect of EHSCF on endothelium-intact and endotheliumdenuded mesenteric rings that were precontracted with Phe (10 μmol/L) or 80 mM KCl. During the tonic phase of the contraction, EHSCF (1 - 1000 mg/L, cumulatively) was added to the organ bath. All analysis was performed using GraphPadTM Prism 3.0 version software
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