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Nerve growth factor protects against cadmium-induced hypertension in mice via vascular remodeling
Abstract
Purpose: To investigate the effect of nerve growth factor (NGF) on cadmium ion (Cd2+)-induced hypertension in a mouse model, and the mechanism of action involved.
Methods: Hypertension was induced in mice by administration of cadmium chloride (CdCl2) at a dose of 100 mg/L in deionised water. Then, NGF was administered daily for 45 days via the intragastric route. Immunohistochemical technique employing Vectastain ABC kit was used for determination of the levels of matrix metalloproteinases in mice aorta.
Results: Treatment with NGF significantly and dose-dependently alleviated Cd-induced increase in blood pressure in mice (p < 0.05). The Cd-induced elevation in mean arterial pressure (MAP) in mice was also reduced on treatment with NGF at doses of 5 and 10 mg/kg. At the two doses of NGF, vascular responsiveness was enhanced in Cd-administered mice. Exposure to NGF dose-dependently reversed Cd-mediated suppression of eNOS expression and elevation in iNOS level. Moreover, NGF at doses of 5 and 10 mg/kg, reversed Cd-mediated enhancement in nitrate/nitrite levels in urine samples, and reversed Cd-induced elevation in vascular smooth muscle cell (VSMC) count and collagen content in mice arterial wall. The NGF treatment also significantly (p < 0.05) reduced Cd-induced increases in levels of MMP’s.
Conclusion: The present study demonstrates that NGF increased vascularity and arterial stiffness, and protected against Cd-induced hypertension in mice. Moreover, NGF treatment elevated eNOS expression, suppressed iNOS level and inhibited MMP expression in mice exposed to Cd. Thus, NGF has anti-hypertensive potential and may be beneficial in the treatment of hypertension.