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 betwee n vasoconstrictor-antinatriuretic and vasodilator-natriuretic forces i s a key feature of the pathophysiology of CHE This review summarizes c urrent understanding of disturbances in vasodilator-natriuretic system s in CHF. The key vasodilator systems involved are: the natriuretic pe ptide family atrial natriuretic peptide (ANP), brain natriuretic pepti de (BNP), urodilatin, dopamine (DA), endothelium-derived relaxing fact ors and prostaglandins. Renal responses to ANP are blunted in CHE unde r the influence of haemodynamic, neuro-humoral, receptor and post-rece ptor events. BNP, secreted in response to left ventricular load, may c irculate in high concentrations in CHF, with similar effects to ANP. U rodilatin is a newly discovered peptide of renal origin whose physiolo gical role is under investigation. Neural endopeptidase inhibitors hav e shown some promise in the treatment of human CHE particularly when c ombined with ACE inhibition or angiotensin II receptor blockade. The r enal DA system is influenced by sodium intake and DA metabolism is alt ered in CHE The place of orally active DA prodrugs and DA agonist in t he management of patients with CHF is still undecided. In CHF, basal r elease of nitric oxide may be preserved or even enhanced. However, sti mulated release of nitric oxide may be reduced. Renal effects of nitri c oxide or arginine in CHF have yet to be defined. Renal prostaglandin s play an important role in offsetting renal and systemic vasoconstric tion and fluid retention in CHE The recent availability of specific re ceptor antagonist should lead to clearer definition of the relative ro les of renal angiotensin II inhibition and bradykinin potentiation in the beneficial responses to angiotensin converting enzyme (ACE-I) in C HF. 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 g ene-related peptide family, is present in high concentrations in the k idney. Plasma concentrations of adrenomedullin are increased after acu te cardiac injury and in CHF. Its roles in renal physiology and in the pathophysiology of CHF are under investigation. Overall, there is con siderable potential to exploit these vasodilator-natriuretic systems i n management strategies for CHF.