Pharmacokinetic, hemodynamic and neurohormone effects of calcium antagonists in sympathetic activation

Neurohormone activation has long been considered a potential for serious adverse effect for calcium antagonists. Clinical studies have shown that the first generation calcium antagonists (CCBs), particularly the short acting nifedipine, may increase the risk of heart attacks and mortality in post myocardial infarct patients; however, the longer acting CCBs are less prone to sympathetic activation and hence could be considerably safer for treatment of hypertension. The primary objective of the proposed research is to study and compare between the short acting CCB with the longer acting ones for their effect on neurohormone activation using a novel exercise rat model developed in our laboratory. In addition, the study also investigates the potential synergistic interactions between the CCBs and other classes of cardiovascular drugs. Each rat under study will receive one of the CCBs and exercise on a treadmill in order to determine the effect of these drugs on the neurohormone response to exercise. These studies will provide valuable insight to further our understanding of the safety and efficacy of this very important and widely used class of cardiovascular drugs for chronic management of hypertension and related cardiovascular diseases.