Acute effects of sildenafil on flow mediated dilatation and cardiovascular autonomic nerve function in type 2 diabetic patients

Background Sildenafil, frequently used as on demand medication for the treatment of erectile dysfunction (ED), has been suggested to improve endothelial function but also to alter blood pressure (1313) and induce sympathetic activation. in people with type 2 diabetes mellitus (T2DM), a high-risk population, the safety profile and the effects on endothelial function of a maximal sildenafil dose (100 mg) have not been investigated and therefore constituted the aim of our study. Methods A double-blind, placebo-controlled, cross-over trial using a single dose of 100 mg sildenafil or placebo has been conducted in 40 subjects with T2DM without known CVD. Haemodynamic parameters, flow mediated dilatation (FMD) in brachial artery, cardiovascular autonomic function tests and spontaneous baroreflex sensitivity (BRS) were measured. Results Sixty minutes after administration of sildenafil but not placebo, a fall of supine systolic blood pressure (SBP) (-5.41 +/- 1.87 vs. +0.54 +/- 1.71 mmHg) and diastolic blood pressure (DBP) (-4.46 +/- 1.13 vs. +0.89 +/- 0.94 mmHg), as well as orthostatic SBP (-7.41 +/- 2.35 vs. +0.94 +/- 2.06 mmHg) and DBP (-5.65 +/- 1.45 vs. +1.76 +/- 1.00 mmHg) during standing occurred, accompanied by an increase in heart rate (+1.98 +/- 0.69 vs. -2.42 +/- 0.59 beats/min) (all p < 0.01 vs. placebo). Changes in BP to standing up, FMD, time domain and frequency domain indices of heart rate variability (HRV) and BRS were comparable between sildenafil and placebo. Conclusions Sildenafil administered at a maximum single dose to T2DM men results in a mild increase in heart rate and decrease in BP, but it induces neither an acute improvement of FMD nor any adverse effects on orthostatic BP regulation, HRV and BRS. Copyright (C) 2008 John Wiley & Sons, Ltd.