Effect of Regular Phosphodiesterase Type 5 Inhibition in Hypertension

There are no published controlled clinical trials of regular phosphodiesterase type 5 inhibitor therapy as a long-term treatment of hypertension. In a randomized, double-blind, 2-way crossover study, 25 otherwise untreated hypertensive subjects were administered 50 mg of sildenafil or matched placebo 3 times daily for 16 days, and the effects on ambulatory blood pressure (BP), clinic BP, arterial wave reflection, carotid-femoral pulse wave velocity, and brachial artery flow-mediated dilatation were assessed. Three subjects were withdrawn because of adverse effects, and the data from the remaining 22 subjects were analyzed. Sildenafil reduced ambulatory BP (mean SE change from baseline for average daytime BP: systolic -8 2 mm Hg versus 2 2 mm Hg with placebo, P<0.01; diastolic -6 1 mm Hg versus 0 1 mm Hg, P<0.01) and clinic BP (change from baseline to 1 hour after drug administration on day 16: systolic -5 2 mm Hg versus 4 2 mm Hg, P<0.01; diastolic -5 1 mm Hg versus 2 2 mm Hg, P<0.01). Compared with baseline, sildenafil, but not placebo, reduced arterial wave reflection both acutely and after chronic treatment, but the chronic change in arterial wave reflection was not statistically different from the chronic change with placebo. Sildenafil did not affect pulse wave velocity or flow-mediated dilatation. The main adverse effects of sildenafil, which were generally transient and rated as mild or moderate in severity, were dyspepsia, headache, and myalgia. In conclusion, regular sildenafil constitutes effective antihypertensive therapy. Further studies are warranted to evaluate the role of longer-acting phosphodiesterase type 5 inhibitors as antihypertensive agents in clinical practice.