The kidney in heart failure: Vasodilator-natriuretic systems

Congestive heart failure (CHF) is a complex clinical syndrome in which the kidney has a central pathophysiological role. An imbalance between vasoconstrictor-antinatriuretic and vasodilator-natriuretic forces is a key feature of the pathophysiology of CHE This review summarizes current understanding of disturbances in vasodilator-natriuretic systems in CHF. The key vasodilator systems involved are: the natriuretic peptide family atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), urodilatin, dopamine (DA), endothelium-derived relaxing factors and prostaglandins. Renal responses to ANP are blunted in CHE under the influence of haemodynamic, neuro-humoral, receptor and post-receptor events. BNP, secreted in response to left ventricular load, may circulate in high concentrations in CHF, with similar effects to ANP. Urodilatin is a newly discovered peptide of renal origin whose physiological role is under investigation. Neural endopeptidase inhibitors have shown some promise in the treatment of human CHE particularly when combined with ACE inhibition or angiotensin II receptor blockade. The renal DA system is influenced by sodium intake and DA metabolism is altered in CHE The place of orally active DA prodrugs and DA agonist in the management of patients with CHF is still undecided. In CHF, basal release of nitric oxide may be preserved or even enhanced. However, stimulated release of nitric oxide may be reduced. Renal effects of nitric oxide or arginine in CHF have yet to be defined. Renal prostaglandins play an important role in offsetting renal and systemic vasoconstriction and fluid retention in CHE The recent availability of specific receptor antagonist should lead to clearer definition of the relative roles of renal angiotensin II inhibition and bradykinin potentiation in the beneficial responses to angiotensin converting enzyme (ACE-I) in CHF. Prostaglandin-E1 (PG-E-1) and prostaglandin-E-2 (PG-E-2) infusion may have some benefit for the treatment of severe CHF. Adrenomedullin, a vasodilator-natriuretic peptide closely related to the calcitonin gene-related peptide family, is present in high concentrations in the kidney. Plasma concentrations of adrenomedullin are increased after acute cardiac injury and in CHF. Its roles in renal physiology and in the pathophysiology of CHF are under investigation. Overall, there is considerable potential to exploit these vasodilator-natriuretic systems in management strategies for CHF.