Reflex systemic sympatho-neural response to brachial adenosine infusion in treated heart failure

Aims In healthy men, brachial artery adenosine infusion elicits a reflex increase in total body norepinephrine (NE) spillover (TBS) that is blunted by oral angiotensin AT(1) receptor blockade. Our objectives were to determine whether a similar reflex is active in treated heart failure (HF) patients and attenuated by ARB. Methods and results In this double-blind study, 12 patients with an ejection fraction <= 40% were randomized to 2 weeks of oral candesartan up-titrated to 32 mg/day or placebo. Forearm blood flow was measured bilaterally by venous occlusion plethysmography. Total body NE spillover was determined following infusion of tritiated NE. After saline was infused into the non-dominant brachial artery to establish baseline values, adenosine and nitroprusside (as vasodilator control) were administered in random order. Both caused dose-dependent increases in ipsilateral but not contralateral blood flow. Nitroprusside had no TBS effect, whereas adenosine reduced TBS from 3967 (SD 2362) to 3293 pmol/min (SD 2093) (P = 0.03). This decrease was not augmented in candesartan-treated subjects [-1096 (SD 726) vs. 2253 pmol/min (SD 1094); placebo vs. candesartan; P = 0.22]. Conclusions In contrast to healthy men, in treated HF patients, locally infused adenosine does not elicit a reflex sympatho-excitatory response mediated by angiotensin AT(1)-modulated neurotransmission.