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Neuropeptide Y (NPY) is coreleased with norepinephrine and stimulates vasoconstriction, vascular and cardiomyocyte hypertrophy via Y1 receptors (R) and angiogenesis via Y2R. Although circulating NPY is elevated in heart failure, NPY's role remains unclear. Activation of the NPY system was determined in Wistar rats with the aortocaval (A-V) fistula model of high-output heart failure. Plasma NPY levels were elevated in A-V fistula animals (115.7 [+ or -] 15.3 vs. 63.1 [+ or -] 17.4 pM in sham, P < 0.04). Animals either compensated [urinary [Na.sup.+] excretion returning to normal with moderate disease (COMP)] or remained decompensated with severe cardiac and renal failure (urinary [Na.sup.+] excretion Y1 receptor; Y2 receptor; renal blood flow; cardiac hypertrophy