[Pathophysiology of cardiorenal regulatory mechanisms in heart failure]

The sympathetic activity in cardiac failure is elevated by excitatory afferents from underperfused muscle and from chemoreceptors, and by attenuated inhibitory control via arterial and cardiopulmonary baroreceptors. Together with renal hypotension, the sympathetic activity activates the renin-angiotensin-system, which in turn enhances sympathetic activity. Together, both systems induce a vicious cycle of further cardiac overload by vasoconstriction, volume retention, and formation of edemas, while beta-adrenergic responsiveness of the heart is depressed. The glomerular filtration rate in the kidney is preserved by efferent arteriolar constriction in the face of reduced renal perfusion. Since circulating angiotensins are preferentially formed by angiotensin-forming systems in the tissues, one has to assume strong local effects of angiotensin II at the site of its synthesis. These local effects cannot exactly be quantified from parameters of the circulating RAS. In the heart, myocardial stretch and neuroendocrine activity (via myocardial angiotensin- and alpha 1-receptors) induce a dedifferentiating growth of cardiocytes. This results in an improved economy of myocardial contraction, but also in delayed relaxation with the risk of Ca(++)-overload and generation of arrhythmias by late after-depolarizations. Probably, enhanced intracardiac formation of angiotensin contributes to these dangerous changes.