Effect of eprosartan on catecholamines and peripheral haemodynamics in subjects with insulin-induced hypoglycaemia

ANG II (angiotensin II) facilitates catecholamine release from the adrenal medulla and neuronal NE (noradrenaline) release. Since animal experiments point to specific sympatho-inhibitory properties of the AT(I) (ANG II type I)-receptor blocker EPRO (eprosartan), the primary aim of this study was to clarify if EPRO inhibits sympathetic reactivity in humans as determined by the effect of EPRO on insulin-induced catecholamine release. Sixteen healthy male volunteers were randomized in a double-blind cross-over study to receive a single dose of EPRO (600 mg) compared with placebo, followed by insulin-induced hypoglycaemia [0.15 IU (international unit)/kg of body weight; intravenous bolus] on two study days 1 week apart. From baseline to the end of hypoglycaemia (170 min), the sympatho-adrenal reactivity was mapped by invasive continuous blood pressure monitoring and repeated measurements of FBF (forearm blood flow), arterial and venous concentrations of glucose, catecholamines [EPI (adrenaline) and NE (noradrenaline)], renin, ANG II and aldosterone. EPRO induced an 8-10-fold increase in plasma renin and ANG II concentrations compared with placebo. Plasma glucose decreased equally during placebo and EPRO from baseline 5.9 mmol/l to 1.9 mmol/l and 2.1 mmol/l respectively, inducing a 17-fold increase in arterial EPI concentration at peak. The AUC (area under the curve) during hypoglycaemia for arterial EPI concentrations was 314 +/- 48 nmol (.) min (.) 1(-1) in placebo compared with 254 +/- 26 nmol (.) min (.) 1(-1) following EPRO treatment (P = 0.14). EPRO attenuated the corresponding AUC for the EPI-induced pulse pressure response (4670 +/- 219 mmHg (.) min in EPRO compared with 5004 +/- 266 mmHg (.) min in placebo; P = 0.02). Moreover, EPRO caused a less pronounced increase in FBF compared with placebo (402 +/- 30 compared with 479 +/- 46 ml (.) 100 g(-1) of body weight; P = 0.04). Musculocutaneous NE release was not affected by EPRO and the AUC for NE release was 51.69 +/- 15.5 pmol (.) min(-1) (.) 100 g(-1) of body weight in placebo compared with 39.35 +/- 18.2 pmol (.) min(-1) (.) 100 g(-1) of body weight after EPRO treatment (P = 0.57). In conclusion, EPRO did not significantly inhibit sympathetic reactivity compared with placebo; however, it blunted the haemodynamic responses elicited by the sympatho-adrenal stimulation which only tended to be attenuated by this drug.