New Therapeutic Options in Congestive Heart Failure: Part I

Neurohumoral Pathways

Over the past 20 years, the “neurohumoral hypothesis” has evolved to focus less on the impact of these pathways on the blood vessels and kidneys and more on the heart (Figure 1, and see below).⁵ This in part reflects the benefit of β-blockers and spironolactone, treatments that are not vasodilators.^6–10⇓⇓⇓⇓ New peptides, such as the endothelins, and other mediators that are not conventional endocrine, autocrine, or paracrine factors, such as cytokines and free radicals, have also been postulated to play a role in CHF.^11,12⇓ These, in turn, are now thought to set into motion pathophysiological processes, such as apoptosis, that had not yet been recognized when the neurohumoral model was originally postulated (Figure 1B).¹³ The interaction between primitive neurohumoral reflexes designed to maintain blood volume and vital organ perfusion and hemostasis has been belatedly recognized.¹⁴