Sinapic Acid Attenuates Cardiovascular Disorders in Rats by Modulating Reactive Oxygen Species and Angiotensin Receptor Expression

Abstract

The main avoidable risk factor for cardiovascular conditions is high blood pressure (hypertension). At global level, hypertension is believed to be responsible for a 54% stroke-related mortality rate and a 47% mortality rate associated with coronary heart disease. It is postulated that sinapic acid (SA) could help in hypertension management because it displays robust antioxidant, antihyperglycemic, and peroxynitrite scavenging effects. To explore this hypothesis, this work examined the effect of SA on oxidative stress and cardiovascular disease in rats with hypertension by comparison against captopril. For this purpose, 50 male rats were used and equally allocated to five groups, namely, normal control, positive control (L-NAME), L-NAME with concomitant captopril administration, L-NAME with concomitant SA administration, and L-NAME with concomitant administration of both SA and captopril. Results showed that, by contrast to control, L-NAME exhibited marked elevation in serum CK-MB, total cholesterol, triglycerides, VLDL-C, LDL-C, Ang II, AT2R, ET-1, and angiopoietin-2; on the other hand, L-NAME exhibited marked reduction in serum HDL-C, superoxide dismutase (SOD) activity, nitric oxide synthase 3 (NOS3), and glutathione (GSH). Furthermore, joint administration of SA and captopril ameliorated hypertension, enhanced cardiovascular function, hindered hyperlipidemia, and decreased oxidative stress and myocardial hypertrophy displayed by rats with hypertension. Based on such findings, better chemopreventive or therapeutic approaches can be devised to manage hypertension and cardiovascular conditions.

Figure 1

Effect of sinapic acid and captopril treatment upon angiotensin II, angiotensin II type 2 receptor (AT2R), endothelin-1, and angiopoietin-2 in different experimental groups. Values are expressed as means ± SD of 10 rats for each group. ^aSignificant difference from the control group. ^bSignificant difference from the L-NAME group. ^cSignificant difference from the L-NAME and sinapic acid (SA)group. ^dSignificant difference from the L-NAME and captopril group. P values ≤ 0.05 were considered significant.

Figure 2

Effect of sinapic acid and captopril treatment upon CK-MB and troponin I in different experimental groups. Values are expressed as means ± SD of 10 rats for each group. ^aSignificant difference from the control group. ^bSignificant difference from the L-NAME group. ^cSignificant difference from the L-NAME and sinapic acid (SA) group. ^dSignificant difference from the L-NAME and captopril group. P values ≤ 0.05 were considered significant.

Figure 3

Effect of sinapic acid and captopril treatment upon oxidative stress in different experimental groups. Values are expressed as means ± SD of 10 rats for each group. ^aSignificant difference from the control group. ^bSignificant difference from the L-NAME group. ^cSignificant difference from the L-NAME and sinapic acid (SA) group. ^dSignificant difference from the L-NAME and captopril group. P values ≤ 0.05 were considered significant.

Figure 4

Gene expression of angiotensin II receptors (AT1A, AT1B, and AT2) of treatment groups compared to nontreated control group (relative to GAPDH (RQ)), using the 2^-ΔΔCT method.

Figure 5

Photomicrographs of rat heart sections in the different experimental groups stained with haematoxylin and eosin. (a) Left ventricular section in the control group showing normal myofibrillar structure with striations. (b, c) Left ventricular sections in the L-NAME group (G2) revealed marked myocardial hypertrophy (black arrows) and nuclear pyknosis (white arrows). (d) Left ventricular sections in the L-NAME+SA (G3) group revealed moderate tissue injury with moderate myocardial hypertrophy (black arrows) and mild cytoplasmic vacuoles with nuclear pyknosis (white arrows). (e) Left ventricular sections in the L-NAME+captopril (G4) group revealed mild myocardial hypertrophy. (f) Heart sections in the L-NAME+SA+captopril (G5) group revealed normal myofibrillar structure with striations as in the control group.