Various pathophysiological mechanisms have been implicated in hypertension, but those resulting in vascular dysfunction and remodeling are critical and may help to identify critical pharmacological targets. This mini-review article focuses on central mechanisms contributing to the vascular dysfunction and remodeling of hypertension, increased oxidative stress and impaired nitric oxide (NO) bioavailability, which enhance vascular matrix metalloproteinase (MMP) activity. The relationship between NO, MMP and oxidative stress culminating in the vascular alterations of hypertension is examined. While the alterations of hypertension are not fully attributable to these pathophysiological mechanisms, there is strong evidence that such mechanisms play critical roles in increasing vascular MMP expression and activity, thus resulting in abnormal degradation of extracellular matrix components, receptors, peptides, and intracellular proteins involved in the regulation of vascular function and structure. Imbalanced vascular MMP activity promotes vasoconstriction and impairs vasodilation, stimulating vascular smooth muscle cells (VSMC) to switch from contractile to synthetic phenotypes, thus facilitating cell growth or migration, which is associated with the deposition of extracellular matrix components. Finally, the protective effects of MMP inhibitors, antioxidants and drugs that enhance vascular NO activity are briefly discussed. Newly emerging therapies that address these essential mechanisms may offer significant advantages to prevent vascular remodeling in hypertensive patients.

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Elevated blood pressure is a leading global contributor to death and disability worldwide, and in 2010, about 1.4 billion people were hypertensive. 1 Hypertension involves a complex interplay of environmental and pathophysiological factors that affect multiple systems and is the most common risk factor that predisposes to cardiovascular diseases. 2 Through its effects on target organs, hypertension has been associated with a variety of cardiovascular comorbidities such as coronary artery disease, stroke, chronic kidney disease, metabolic syndrome and dyslipidaemia. 3 Maintenance of normal blood pressure is dependent on the balance between the cardiac output and vascular resistance.

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