W. Raasch et al., Angiotensin converting enzyme inhibition improves cardiac neuronal uptake of noradrenaline in spontaneously hypertensive rats, J HYPERTENS, 19(10), 2001, pp. 1827-1833
Citations number
50
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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.