Investigation of antihypertensive mechanism of garlic in 2K1C hypertensive rat

Abstract

This study sought to examine the antihypertensive mechanism of garlic in two-kidney-one-clip (2K1C) hypertensive rat. In this study, the effect of garlic on serum and tissue including: aorta, heart, kidney, lung as well as circulatory (serum) ACE activity in 2K1C rats were examined.

Four groups of rats were selected: control “CTL”, sham-operated “SHAM”, hypertensive “H” and garlic-treated hypertensive “GT” group. Hypertension was induced by surgery. Four weeks post-clipping, single daily dose of 50 mg of aqueous extract of garlic was given orally to “GT” rats for 4 weeks. Blood pressure was measured by tail-cuff method.

ACE activity was determined using HPLC. The systolic blood pressure (SBP) was significantly increased in “H” compared to “CTL” group. In “GT” group, blood pressure was significantly decreased compared to “H” group. The ACE activity in all tissues of “H” group was significantly increased compared to controls which was significantly decreased in garlic-treated compared to non-treated hypertensive rats. These results indicated a negative correlation between consumption of garlic, blood pressure and ACE activity in serum and different tissues in 2K1C rats, suggesting that garlic has a significant blood pressure lowering effect, which could partly be mediated by reduction in ACE activity.

Introduction

Garlic (Allium sativum L.) has long and widely been used not only as a flavoring agent but also as a folk medication.

There is compelling evidence, suggesting various pharmacological properties of garlic opposing microbial infection, thrombosis, hypertension, hyperglycemia, hyperlipidemia, cancer as well as being a healing agent (Pedraza-Chaverri et al., 1998).

Garlic preparations contain a wide variety of organosulfur compounds in which allicin is the most notable and it is responsible for the characteristic garlic odor. Allicin and other thiosulfinates are found in crushed, chewed or chopped garlic when cellular membrane is disrupted. This brings the precursor compound Allicin (S-allyl-l-cysteine sulfoxide) in contact with the enzyme “Allinase” (Jansen et al., 1989, Yu et al., 1989).

Several reports have also suggested that fresh garlic extract has protective actions against cardiovascular disorders including: stroke, coronary artery disease, arteriosclerosis and hypertension (Bordia et al., 1977, Bordia et al., 1978, Chutani and Bordia, 1981). These beneficial effects have partly been attributed to its ability to inhibit platelet aggregation and thromboxane formation (Bordia, 1978, Makheia et al., 1979, Samson, 1982). Blood pressure lowering effect of garlic has been reported not only in spontaneously hypertensive rats (Foushee et al., 1982, Samson, 1982), 2K1C rats (Al-Qattan et al., 1999) and hypertensive patients (Zheziang Institute of Traditional Chinese Medicine, 1986) but also in normotensive animals (Banerjee, 1979).

Various mechanisms for antihypertensive effect of garlic are being reported including: hyperpolarization of human coronary artery by opening K⁺ channels as well as stimulation of nitric oxide synthesis (Pedraza-Chaverri et al., 1998) causing vasodilatation.

The rennin–angiotensin–aldosteron system (RAAS) plays an important role in the control of cardiovascular homeostasis affecting both blood pressure and fluid volume and is one of the most important etiological candidates in hypertension (Sealy and Laragh, 1995). It is now well documented that all the components of this enzymatic pathway may reside within several individual organs or tissues such as kidneys, lung, heart and vascular smooth muscle cells (Dzau, 1988). The presence of angiotensin-converting enzyme (ACE) and other components of rennin–angiotensin system in arteries indicates that angiotensin II can be locally formed in the arterial wall, inducing both structural and functional changes in hypertension (Saavedra et al., 1992) and plays an important role in elevation of peripheral vascular resistance (Li et al., 1997). It has been known that arterial ACE is high in both genetic (Nakata et al., 1987, Nakamura et al., 1988) and experimental (Miyazaki et al., 1988) models of hypertension in rat and it is correlated with elevation of blood pressure (Nakata et al., 1987). Moreover, ACE inhibitors are one of the widely used antihypertensive drugs in the treatment of patients with essential and renovascular hypertension (Unger et al., 1990).

Using herbal medications instead of chemical drugs because of minor side effects have always been one of the wishes of human being for years. In spite of important role of garlic in prevention and controlling cardiovascular disorders, its precise mechanism of action is unknown.

The present study, therefore, investigated the antihypertensive mechanism of garlic in 2K1C hypertensive rats by measurement of circulatory and local ACE activity in aorta, heart, kidney and lung.