Kinases mediate the phosphorylation of a wide variety of proteins and compounds in the cell. Along with phosphatases, kinases are involved in a range of regulatory pathways. Given the physiological importance of kinases, they have been subject to intense scrutiny, and are proven drug targets.
Hypertension, or high blood pressure, is a major public health problem, and is defined as the condition of having blood pressure (BP) exceeding an upper limit of normality. In humans, the upper limit is generally accepted as a systolic BP of greater than 140 mg Hg and/or diastolic BP of greater than 90 mg Hg. In the majority of cases, patients are affected by essential hypertension, which by definition means that the underlying etiologic mechanism(s) causing the hypertension is unknown. Regardless of the mechanism, a sustained elevation of blood pressure for a period of time has been shown to result in significant cardiovascular damage throughout the body, e.g., congestive heart failure, coronary artery disease, stroke, kidney failure, and progressive renal failure. Hypertension is believed to affect 60 million people in the United States, and believed to account for approximately 50% of mortality beyond age 65.
It is generally accepted that a significant elevation of blood pressure can accelerate the aging process in the circulatory system. During aging, many factors involved in regulating blood pressure can go awry. Therefore it is not surprising that systolic and diastolic blood pressure increase progressively with aging, a phenomenon which is called “age-related hypertension”. Hypertension is found in 50% or more of individuals above age 55 years, and 63% of those age 65 to 74 years. The rate is 76% among persons of African origin over 65 years old in the United States. This age-related hypertension, particularly of the diastolic blood pressure, is most likely due to the reduced elasticity of the blood vessels or, even worse, stiffness of the blood vessels. This reduced elasticity may be caused by damage of the muscle layer of the blood vessels. This damage can be caused by radicals from chemicals, radiation or other toxins. Due to this, these endothelial muscles cannot function properly in contracting and relaxing when blood pressure demand makes that necessary. The consequence is a higher diastolic blood pressure.
There are numerous substances in use against higher blood pressure, such as angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, calcium-antagonists, diuretics, vasodilatators, and combinations thereof. However, currently available anti-hypertensive agents are not without side effects, such as the elevation of blood lipids and glucose. The elevation of blood lipids and glucose by these agents has been suggested as a reason why anti-hypertensive agents have not demonstrated any benefit to patients being monitored in death rate studies.
Therefore, there exists an outstanding need to develop new drugs to treat hypertension.