Neurohumoral mechanisms in heart failure: role in pathogenesis, therapy, and drug tolerance.
Animal models of experimental heart failure have provided the basis of our current understanding of the role of the kidney and neurohumoral mechanisms in clinical congestive heart failure (CHF). The vasoconstrictor hormones, i.e., the renin-angiotensin system (RAS) and the sympathoadrenal and vasopressin systems, are activated in acute cardiac decompensation and are essential for the maintenance of systemic blood pressure. With expansion of extracellular fluid volume and restoration of blood pressure, these vasoconstrictor systems return to normal during chronic stable CHF. During cardiac decompensation, vasodilator prostaglandins (PG) I2 and E2 are also activated and may play a modulating role in the regulation of organ perfusion and function. Indeed, close correlations exist between plasma renin activity, plasma angiotensin II, and PGE2 metabolite concentration (r = 0.72 and 0.84, respectively). Based on our understanding of the neurohumoral mechanism in the regulation of vasculature in clinical CHF, alpha-adrenergic antagonists and inhibitions of the RAS have been used successfully as vasodilators in the therapy of CHF. Finally, recent observations also indicate that primary or secondary activation of these neurohormonal compensatory mechanisms can explain, in part, the development of tolerance to vasodilator therapy in CHF.
D000804:Angiotensin II / Q000097:blood; D001806:Blood Urea Nitrogen; D002216:Captopril / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004361:Drug Tolerance; D005110:Extracellular Space; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000627:therapeutic use
D014665:Vasodilator Agents; D000804:Angiotensin II; D002216:Captopril; D003404:Creatinine; D012083:Renin