Eprosartan decreases the pulse pressure response to sympathoadrenal activation in humans

Abstract

Angiotensin II facilitates catecholamine release from the adrenal medulla and neuronal norepinephrine release. Animal experiments suggest that the non-biphenyl AT1-blocker eprosartan (EPRO) might possess specific sympathoinhibitory properties. We aimed to clarify if EPRO inhibits sympathetic reactivity in humans. 16 healthy male volunteers participated in a randomized double-blind cross-over study to receive a single dose EPRO of 600 mg vs. placebo followed by insulin-induced hypoglycemia [i.v. bolus; 0,15IU/kg] on two study days one week apart. The hypoglycemia-induced sympathoadrenal reactivity was mapped by invasive continuous blood pressure monitoring and frequent measurement of forearm blood flow (FBF), arterial and venous concentrations of glucose, catecholamines epinephrine and norepinephrine (EPI; NE), renin (PRC) and angiotensin II (AngII). Acute AT1-receptor blockade was effective since EPRO induced a 8–10 fold increase of circulating PRC and AngII. Plasma glucose decreased equally during placebo and EPRO from baseline 5,9 mM to 1,9 mM during which circulating EPI increased about 12 fold. Musculocutaneous NE release was unaltered during EPRO compared to placebo while the cumulative measure of adrenal EPI release (AUCEPI) was reduced by 20 % though not statistically significant (P=0,14). However, the EPI-induced pulse pressure response (PPR) was significantly blunted by EPRO: AUCPPR,Placebo = 39920 ± 2000 mmHg5 • min. vs. AUCPPR,EPRO= 37120±1680 mmHg • min. (P=0,0037). Moreover, EPRO tended to inhibit the EPI induced increase of FBF by 13% (P=0.077). The EPRO-induced inhibition of EPI release was not statistically significant. However EPRO highly significantly inhibits the classical EPI-induced pulse pressure response to sympathoadrenal activation. Thus EPRO appears to possess unique though ill-understood sympathoinhibitory properties.