Endogenous digitalis - the long journey from a herbal cardiac toxin to a mammalian hormone.

摘要

Endogenous cardiac glycosides were recently identified in the blood, urine, adrenal glands and hypothalamus of mammals. Such endogenous cardiac glycosides are ouabain, digoxin and marinobufagenin, all well known inhibitors of the sodium pump. The compounds are synthesized in the adrenal cortex with progesterone and pregnenolone as precursors. Physical exercise leads to a rapid increase in ouabain which declines within minutes upon rest. However, treatment with ACE-inhibitors and beta -blockers prevents this increase. Adrenal cortical cells release ouabain rapidly upon treatment with ACTH, angiotensin II and epinephrine. Nanomolar concentrations of ouabain stimulate the proliferation of smooth muscle cells and the release of endothelin 1 from endothelial cells. Dogs suffering from cardiomyopathy have reduced plasma concentrations of endogenous ouabain as compared to healthy dogs. Increased dietary exposure of humans and rats to NaCl results in a parallel increase in endogenous ouabain and arterial blood pressure. Long-term infusion of rats with nanomolar concentrations of ouabain, but not digoxin, results in the development of arterial hypertension. However, digoxin lowers ouabain-induced hypertension. About 50% of the European population suffering from arterial hypertension show elevated concentrations of endogenous ouabain in the blood plasma. Hence it is of considerable importance that rostafuroxin, a ouabain antagonist, effectively lowers blood pressure. Marinobufagenin, which is increased in the blood plasma of human patients with cardiac infarction, induces natriuresis. Ouabain is synthesized in the hypothalamus as well. It is released quite certainly in some areas of the brain upon intracellular increase in sodium..