Angiotensin converting enzyme inhibition improves cardiac neuronal uptake of noradrenaline in spontaneously hypertensive rats

Objectives It has been shown that a diminished sympathetic activity contrib utes to the hypotensive and cardioprotective actions of angiotensin convert ing enzyme (ACE) inhibitors (ACEI). Besides an inhibition of central sympat hetic tone and peripheral noradrenaline release, we hypothesized that the i nteractions of ACEI with the sympathetic system may include a modulation of neuronal catecholamine uptake by peripheral nerves. Design We investigated the influence of fosinopril on noradrenergic uptake into cardiac neurones in vitro and in vivo in acute and chronic models. Methods and results Acute administration of fosinoprilat to isolated perfus ed rat hearts increased the extraction of [H-3]-noradrenaline from the perf usate by 39%. Treatment (14 days) of spontaneously hypertensive rats (SHR) with fosinopril (20 mg/kg per day) enhanced the cardiac uptake of Lv. admin istered [H-3]-noradrenaline by 28%. The endogenous left ventricular content of noradrenaline was increased by 49% after an anti hypertensive treatment of SHR with fosinopril (20 mg/kg per day). Identical increases in cardiac noradrenaline stores (53%) were observed in SHR treated with a blood pressu re ineffective dose of fosinopril (0.2 mg/kg per day). The myocardial conte nt of adrenaline was increased in parallel to noradrenaline after both dose regimes. Conclusions It is concluded that ACEI increases neuronal uptake of catechol amines in SHR in a blood pressure-independent manner. This effect occurs ac utely and is independent of central sympathetic activity. Therefore, we hyp othesize that ACEI modulate the activity of the cardiac noradrenaline trans porter by direct activation. The improved uptake of noradrenaline may contr ibute to the antihypertensive and cardioprotective effects of ACEI (C) 2001 Lippincott Williams & Wilkins.