Venous neuropeptide Y receptor responsiveness in patients with chronic heart failure

Background Chronic heart failure is associated with increased sympathetic nerve activity and elevated plasma neuropeptide Y levels. The aim of this study was to investigate whether increased neuropeptide Y release altered vascular neuropeptide Y responses in the dorsal hand veins in patients with chronic heart failure. Methods and results Neuropeptide Y responsiveness was studied in vivo with use of a hand vein tonometry technique in 14 patients with chronic heart failure and left ventricular ejection fraction (LVEF) values <20%, 16 patients with LVEF values from 20% to 35%, and 16 age‐similar healthy control subjects. Plasma norepinephrine and neuropeptide Y levels were significantly elevated in patients with chronic heart failure and LVEF values <20% compared with control subjects ( P < .01). Plasma neuropeptide Y but not norepinephrine levels were significantly elevated in patients with chronic heart failure and LVEF values from 20% to 35% compared with control subjects ( P < .01). Increasing doses of neuropeptide Y (25 to 2000 pmol/min) were infused into a dorsal hand vein of each subject. Dose‐dependent venoconstriction to neuropeptide Y was observed in all subjects studied. The neuropeptide Y dose‐response curve in patients with LVEF values from 20% to 35% was significantly shifted to the left compared with patients with LVEF values <20% and control subjects ( P < .01), whereas no significant difference was observed between the control subjects and the patients with LVEF values <20%. No significant difference in neuropeptide Y dose responses was observed between patients with chronic heart failure with plasma neuropeptide Y levels above the median and patients with chronic heart failure with plasma neuropeptide Y levels below the median. Conclusions In vivo venous neuropeptide Y receptor responsiveness is increased in patients with chronic heart failure and LVEF values from 20% to 35%. This increased neuropeptide Y responsiveness may contribute to venoconstriction at this stage of heart failure. (Clin Pharmacol Ther 2000;67:292–8.) Clinical Pharmacology & Therapeutics (2000) 67 , 292–298; doi: 10.1067/mcp.2000.104610