Antihypertensive potential of thymoquinone in normal and L-NAME induced hypertensive rats

Abstract

Introduction: Hypertension is one of the leading causes of death due to stroke and heart diseases, Nigella sativa “black cumin” seeds have been widely used in traditional medicine for diseases treatment including hypertension. Thymoquinone (TQ) is one of the major active constituents in its volatile oil. Objective of this study was to evaluate the antihypertensive potential of TQ and to investigate the underlying mechanisms of action. Method: In normotensive rats; mean arterial blood pressure (MAP) and heart rate (HR) was recorded using the non-invasive tail cuff technique. Dose-response relationship was obtained by using 3 TQ doses (2.5, 5 and 10 mg/kg) intraperitoneally to 3 different groups (n=5) of adult male Sprague-Dawley rats under pentobarbital anesthesia. MAP was then measured for other two animal groups pretreated either with atropine (P-at) or propranolol (P-pro) followed by 10 mg/kg TQ. Hypertension was induced in another group of animals (n=36) and control (n=6) by administration of L-Nitro-Arginine Methyl Ester (L-NAME) in their drinking water for four weeks. At the end of the induction period, rats were divided into six groups (n=8); TQ2.5+L-NAME, TQ5+L-NAME, TQ10+L-NAME, captopril+L-NAME, L-NAME only and control. MAP and HR were recorded by the tail cuff technique weekly for four weeks. Then animals were sacrificed, and blood was collected for determination of ACE activity and aldosterone concentration using ELISA. Lipid profile was assayed twice; at the end of the induction period and the end of the treatment period. Results: TQ produced a dose-dependent blood pressure lowering effect, where 2.5 5 and 10 mg/kg of TQ treatment decreased MAP by 8±1 mmHg, 12±3 and 29±3 mmHg, respectively. TQ-induced MAP reduction was significantly less in P-at than non-pretreated group. Conversely, TQ-induced MAP reduction in P-pro did not demonstrate a significant difference from the non-pretreated group. TQ reversed the established hypertension in TQ5 and TQ10 groups, and prevent further increase in MAP in TQ2.5 group. TQ antihypertensive activity was associated with a decrease in serum aldosterone concentration and an increase in ACE activity. TQ treatment lowered all the blood lipid profile parameters. Conclusion: This study confirms the dose-related hypotensive effect of TQ. The mechanism of TQ-induced hypotension involves at least in part activation of vascular muscarinic receptors, but not ?-adrenergic receptors. The antihypertensive activity of TQ takes place through renin angiotensin aldosterone system.?