It is now becoming clear that two major systems namely the sympathetic nervous system and the renin-angiotensin system are activated in response to ischemic injury; these result in the elevation of plasma catecholamines and angiotensin II during the development of myocardial infarction as well as congestive heart failure. Although plasma levels of several other hormones including aldosterone, endothelin, vasopressin, natriuretic peptides, growth factors and inflammatory cytokines are also increased in heart failure, their relationship with changes in catecholamine and/or angiotensin levels as well as their significance for the induction of congestive heart failure are poorly understood. In this article we have examined the evidence regarding the role of endothelin and vasopressin in the pathogenesis of cardiac hypertrophy and congestive heart failure in addition to evaluating the significance of their antagonism by using their receptor blockade for treatment of congestive heart failure. Endothelin appears to maintain blood pressure by its vasoconstricting action whereas vasopressin primarily produces similar effect by retention of body fluid. Myocardium is also known to express both ET-A and ET-B receptors in addition to V1 and V2 receptors for vasopressin, which have been shown to induce cardiac remodeling. Out of various ET-1 receptor antagonists, which are available, a non-selective endothelin receptor antagonist, bosentan, as well as an ET-A receptor antagonist, BQ-123, seem most promising for the treatment of congestive heart failure. Likewise, vasopressin antagonists such as a non-selective antagonist, conivaptan, as well as V2 selective antagonist, tolvaptan, may prove highly valuable for the therapy of this condition. Since most of the existing interventions are helpful in treating patients with congestive heart failure only partially, there appears to be a real challenge for developing some combination therapy for the treatment of congestive heart failure.

Since excessive amounts of catecholamines are known to produce arrhythmias and increase the plasma level of aminochrome, an oxidation product of catecholamines, we tested the hypothesis that antioxidants may reduce the formation of aminochrome and prevent the catecholamine-induced arrhythmias. For this purpose, Sprague-Dawley rats were pretreated orally, with vitamin A or vitamin C for 21 days, and their effects on ventricular arrhythmias induced by a bolus dose or cumulative doses of intravenous epinephrine were examined. Electrocardiogram recording of these animals revealed that pretreatment with either of these vitamins increased the time of onset and decreased the duration of the epinephrine-induced ventricular arrhythmias. Ventricular fibrillations due to high doses of epinephrine were also prevented by the antioxidant pretreatment. Although pretreatment with either vitamin A or vitamin C did not affect the basal malondialdehyde level in control animals, the increase in malondialdehyde level caused by epinephrine administration was significantly reduced by these agents. The elevated level of plasma aminochrome due to epinephrine was also decreased by vitamins A and C treatments. The results indicate that antioxidant may prevent catecholamine-induced arrhythmias by reducing the formation of aminochrome and thus may provide a new strategy for the management of stress-related heart disease.

No abstract