N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs.
Recently, in vivo and in vitro studies have implicated nitric oxide as a mediator of the vascular effects of angiotensin-converting enzyme inhibitors (ACEIs). In the present study we hypothesized that N-acetyl-L-cysteine (NAC), by increasing the availability of reduced sulfhydryl groups, would enhance the antihypertensive response to the ACEIs captopril and enalaprilat by a mechanism dependent on nitric oxide. The experiments were performed on instrumented, indomethacin-pretreated, awake spontaneously hypertensive rats (SHRs). Thirty minutes after a bolus of captopril (10 mg/kg iv) was administered, blood pressure decreased from 167 +/- 5 to 147 +/- 6 mmHg (n = 8). The pretreatment with the donor of thiol groups NAC (300 mg/kg iv) potentiated the depressor response to captopril because blood pressure decreased from 172 +/- 3 to 139 +/- 4 mmHg (n = 6). At the dose of 60 micrograms/kg iv, the ACEI enalaprilat did not acutely modify the blood pressure of SHRs (from 172 +/- 5 to 167 +/- 4 mmHg; n = 6). However, when the SHRs were pretreated with NAC, the same dose of enalaprilat significantly reduced blood pressure from 176 +/- 5 to 151 +/- 5 mmHg (n = 6). This potentiation of the depressor response to ACEIs, due to NAC, was not observed when SHRs were pretreated with the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 50 micrograms.kg-1.min-1 iv). The results of this study suggest that NAC, a donor of sulfhydryl groups, potentiates the antihypertensive response to captopril and enalaprilat in SHR by a nitric oxide-dependent mechanism.
Ruiz
F J
FJ
Departamento de Fisiología Humana, Facultad de Medicina, Murcia, Spain.
Salom
M G
MG
Inglés
A C
AC
Quesada
T
T
Vicente
E
E
Carbonell
L F
LF
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D004357:Drug Synergism; D015773:Enalaprilat / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
D002216:Captopril; D015773:Enalaprilat; D000111:Acetylcysteine