Is neuropeptide Y a contributor to volume-induced hypertension?

Abstract

Hypertension often occurs with fluid overload. The most common mechanism is considered to be mediated by increased cardiac output. Hemodialysis (HD) patients frequently have large amounts of fluid overload. Neuropeptide Y (NPY) is activated by stress and contributes to hypertension and heart failure. We speculated that NPY may be released by the stress of fluid overload and, by its vasoconstrictor effect, may contribute to hypertension and heart failure. Plasma levels of NPY and other vasoconstrictors were studied in 20 HD patients with varying degrees of fluid overload, and the relationship of NPY plasma levels to blood pressure was analyzed. The plasma concentrations of NPY correlated with the degree of fluid overload (r = 0.89; P < 0.0001) and the mean arterial blood pressure (r = 0.85; P < 0.0001). Seven patients had fluid overload of greater than 6% of body weight. They had higher blood pressures and higher plasma concentrations of NPY than 13 HD patients with less than 5% of fluid retention (systolic blood pressure, 179+/-8.2 v 145+/-3.7 mm Hg, P = 0.007; NPY, 61+/-4.6 v 26.8+/-2.7 pmol/L, P < 0.001). In stepwise multiple regression analysis, NPY alone explained blood pressure elevation when analyzed with fluid overload and angiotensin II, renin, noradrenaline, and adrenaline levels. We hypothesized that fluid overload in dialysis patients is a stress-inducing state that activates the sympathetic nervous system and releases the vasoconstrictor NPY. The resulting inappropriate vasoconstriction may contribute to volume-induced hypertension and heart failure in a vicious cycle. We conclude that determination of plasma NPY levels may be useful as a marker of the clinical threat of overhydration.