N -Acetylcysteine Potentiates the Antihypertensive Effect of ACE Inhibitors in Hypertensive Patients

Abstract

Sulfhydryl group donors, such as N -acetylcysteine (NAC), may enhance the antihypertensive effect of some drugs through a nitric oxide (NO) mechanism. It has been observed that the hypotensive effect of angiotensin-converting enzyme inhibitors (ACEIs) is, at least partially, mediated by NO. We performed a within patient crossover study with the aim to investigate the potential effect of NAC on the ACEI antihypertensive action, via an NO-dependent mechanism. We studied 18 smoker (> 10 years of habit and > 10 cigarettes daily) hypertensive patients (15 males and three females, aged 69 - 5 years) on ACEI therapy (11 captopril and seven enalapril). Patients were randomly allocated to two treatment arms. In one arm, the patients ( n = 10) initially received the addition of NAC (600 mg t.i.d.) to the ACEI regimen. In the other group ( n = 8), the patients remained only on ACEI. After 21 days, the therapeutic patterns were crossed. The first group received only ACEI, and the second group received ACEI and NAC and completed other 21-day treatment period. We evaluate the effect of NAC on each patient by ambulatory blood pressure monitoring (ABPM), performed at the end of each therapeutic regimen. A significant decrease in systolic and diastolic 24-h blood pressure (24 hBP) and daytime BP (dtBP) was achieved with the combination of ACEI and NAC (ACEI + NAC) when compared to the period with only ACEI: 24 hBP = 146.1 - 4.2 vs 137 - 3.1 ( p < 0.05) and 89.2 - 2.8 vs 83.5 - 3.7 mmHg ( p = 0.01). DtBP: 149.7 - 5.6 vs 141 - 3.7 and 92.1 - 4 vs 86 - 3.2 (both, p < 0.05). No significant difference was observed in night-time BP (ntBP). The NAC effect was not statistically different for the two ACEIs. In conclusion, the addition of NAC to an ACEI potentiates its antihypertensive effect during 24hBP and dtBP in smoker hypertensives. This effect may be mediated by an NO-dependent mechanism, probably through the protective effect of NAC on NO oxidation.