N-acetylcysteine inhibits angiotensin converting enzyme in vivo.
J Pharmacol Exp Ther
; 265(3): 1239-44, 1993 Jun.
Article
em En
| MEDLINE
| ID: mdl-8389858
ABSTRACT
Nitrate tolerance has been explained by 1) a direct loss of pharmacological effect due to reduced bioconversion and 2) an indirect effect due to activation of the renin/angiotensin system and counter-regulatory vasoconstriction. The sulfhydryl compound N-acetylcysteine (NAC) has been shown to attenuate and partly counteract tolerance to nitrates, and this effect has been attributed to a nitrate/sulfhydryl interaction and increased production of vasoactive intermediates. The effect of NAC on counter-regulatory mechanisms is, however, unknown. This study examined whether NAC modulates the function of the renin/angiotensin system in normal rats and in nitrate-tolerant healthy volunteers. Animal study Conscious rats received NAC (5 mmol/kg/hr i.v., n = 8) or placebo (N-acetylserine, n = 8). Two hours of NAC infusion significantly reduced the pressor effect of angiotensin I (ANG I) by 39 +/- 14% (mean +/- SEM) and reduced angiotensin converting enzyme activity by 31% in plasma (N-acetylserine 74 +/- 9 nmol/min/mg, NAC 51 +/- 7) and 43% in kidney (N-acetylserine 0.9 +/- 0.3, NAC 0.5 +/- 0.1 nmol/min/mg protein) (P < .05). Clinical study Isosorbide dinitrate (5 mg/hr) was infused into six male volunteers for 48 hr. NAC (2 g i.v. followed by 5 mg/kg/hr) was co-infused from 24 to 48 hr. Plasma angiotensin II (ANG II) increased during the first 24 hr of isosorbide dinitrate infusion and decreased from 28 +/- 4 to 14 +/- 2 ng/l after 2 hr of NAC infusion (P < .05). The results suggest that sulfhydryl supplementation modifies the function of the renin/angiotensin system in vivo, an effect probably mediated by inhibition of angiotensin converting enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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Base de dados:
MEDLINE
Assunto principal:
Acetilcisteína
/
Inibidores da Enzima Conversora de Angiotensina
Tipo de estudo:
Clinical_trials
Idioma:
En
Revista:
J Pharmacol Exp Ther
Ano de publicação:
1993
Tipo de documento:
Article
País de afiliação:
Dinamarca