Effect of sildenafil on blood pressure and arterial wave reflection in treated hypertensive men.
As the effects of sildenafil are in part mediated by enhancing the action of nitric oxide and nitrates given acutely markedly reduce early wave reflection, we explored the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure and arterial wave reflection in treated hypertensive men in a single-blind randomised placebo controlled crossover study. Eight men (aged 57-76 years) with well controlled hypertension and erectile dysfunction and no contraindications to the use of sildenafil, were given either sildenafil 50 mg or placebo orally, with the second drug being given 2 weeks later. Blood pressure and heart rate with an automated digital oscillometric device (Omron) HEM-705 CP) and the augmentation index, a measure of arterial wave reflection in the aorta derived using radial applanation tonometry, were measured before and at 15-min intervals for 2 h thereafter. The extent of individual maximum reductions (mm Hg) from baseline in systolic (24 +/- 10 vs. 6 +/- 8, P < 0.05) and diastolic blood pressure (8 +/- 5 vs. 3 +/- 2, P < 0.05) occurred on the sildenafil study day. On average the brachial blood pressure at 75 min following sildenafil was 17/11 mm less than on the placebo day (P < 0.01). Augmentation index was also reduced significantly at 90 min (P < 0.05) suggesting reduced vascular tone in the arteries. The area under the brachial and aortic blood pressure and augmentation index time curve (by the trapezoidal rule corrected for baseline reading) was significantly lower (P < 0.05) on the sildenafil study day. The study shows that the peripheral vasodilatory effects of sildenafil, possibly related to nitric oxide, are accompanied by a fall in systemic blood pressure and reduced arterial wave reflection.
Mahmud
A
A
Department of Pharmacology and Therapeutics, Trinity Centre and Hypertension Clinic, St. James's Hospital, Dublin 8, Ireland.
Hennessy
M
M
Feely
J
J
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004110:Diltiazem / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004347:Drug Interactions; D007172:Erectile Dysfunction / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011673:Pulsatile Flow / Q000187:drug effects*; D011687:Purines; D011945:Receptors, Angiotensin / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D016037:Single-Blind Method; D013450:Sulfones
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011945:Receptors, Angiotensin; D013450:Sulfones; D017311:Amlodipine; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D004110:Diltiazem