The Effect of Antihypertensive Drugs on NADH in Newly Diagnosed Primary Hypertension

Abstract

Background. Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are challenging in humans. We applied a noninvasive forearm skin measurement of the 460-nm fluorescence specific for the reduced form of nicotinamide adenine dinucleotide (NADH) to study the 6-week effects of four different antihypertensive medications on mitochondrial function using the Flow-Mediated Skin Fluorescence (FMSF). Methods. In a prospective open-label study, we compared the long-term effects of a 6-week treatment with either amlodipine (5 mg), perindopril (5 mg), nebivolol (5 mg), or metoprolol (50 mg) on the dynamic flow-mediated changes in the skin NADH content in 76 patients (29 women) with untreated primary arterial hypertension (HA). Patients underwent 24-hour ambulatory blood pressure monitoring. To study mitochondrial function, the FMSF was measured at rest, during 100-second ischemia and postischemic reperfusion. The control group consisted of 18 healthy people (7 women). Results. There were no significant differences in the FMSF parameters between the control and the study group before medication. After the 6-week treatment, all drugs similarly reduced blood pressure. Neither amlodipine, perindopril, nor nebivolol changed the flow-mediated 460-nm skin fluorescence significantly. However, metoprolol raised this fluorescence at rest, during ischemia and reperfusion ( $P$ at most <0.05), indicating an increase in the total NADH skin content. Conclusion. Amlodipine, perindopril, and nebivolol appear neutral for the skin NADH content during the 6-week antihypertensive treatment. Similar treatment with metoprolol increased skin NADH at rest, during ischemia and reperfusion, probably due to an effect on microcirculation and altered mitochondrial function. Explanation of the potential mechanisms behind metoprolol influence on the skin NADH metabolism requires further investigation.