Vascular dysfunction in the coronary and peripheral circulations is an early prognostic marker of future cardiovascular events. Measurements of coronary and peripheral vascular function in resistance vessels can be made, but rely on invasive procedures, which make them unsuitable for routine application. An assessment of the direct correlation between vascular responses in skin and coronary vessels has not been made previously. In 27 normal healthy subjects (18-55 years of age), we examined the relationship between peripheral and coronary vascular function. Cutaneous perfusion was measured using the non-invasive technique of laser Doppler imaging during iontophoresis of acetylcholine and sodium nitroprusside, and cutaneous vascular conductance was calculated (laser Doppler perfusion/mean arterial pressure). Coronary flow reserve was measured using transthoracic echocardiography during intravenous adenosine infusion. Mean diastolic velocities were measured at baseline and peak hyperaemic conditions from the Doppler signal recordings. CVR (coronary velocity reserve) was defined as the ratio of hyperaemic to basal mean diastolic velocities. There were significant positive correlations between CVR and cutaneous vascular conductance for acetylcholine (r=0.399, P=0.039) and sodium nitroprusside (r=0.446, P=0.020). These results support the idea that peripheral measurements of skin blood flow are representative of generalized microvascular function including that of the coronary circulation in normal healthy subjects.

Aims To test the non‐inferiority of a single dose of tadalafil 20 mg compared with placebo with respect to 26‐h mean ambulatory systolic and diastolic blood pressure in treated and untreated hypertensive subjects. Methods A multicentre, randomized, double‐blind, placebo‐controlled crossover study in 114 subjects with hypertension (36 subjects on no therapy with daytime mean ambulatory blood pressure ≥ 140/85 mmHg; 38 subjects on two to four classes of antihypertensive agents with daytime mean ambulatory blood pressure ≥140/85 mmHg and 40 subjects on two to four classes of antihypertensive agents with ambulatory blood pressure < 140/85 mmHg). Results Overall tadalafil reduced mean ambulatory blood pressure monitor systolic and diastolic blood pressure by 4.8 mmHg [95% confidence interval (Cl) 3.7, 5.9; P < 0.01] and 2.9 mmHg (95% CI 1.9, 3.6; P < 0.01), respectively, compared with placebo. In hypertensive subjects with uncontrolled blood pressure on two to four classes of antihypertensive agents (n = 36) tadalafil reduced mean ABPM systolic and diastolic blood pressure by 7.5 mmHg (95% CI 5.4, 9.6; P < 0.01) and 4.3 mmHg (95% CI 6.1, 8.9; P < 0.01) compared with placebo. Conclusions In patients with uncontrolled hypertension on multiple agents the addition of tadalafil 20 mg lowered mean 26‐h blood pressure.

No abstract

ObjectiveTo investigate the effect of tadalafil on the time to exercise-induced myocardial ischaemia in subjects with coronary artery disease (CAD). BackgroundCAD and erectile dysfunction (ED) share similar risk factors. It is impor tant to know the cardiovascular effects of tadalafil in patients with CAD during physical exertion that is comparable with sexual activity. MethodsA randomized, placebo-controlled, double-blind, two-period, crossover study comparing the effects of tadalafil 10 mg and placebo on the time to exercise treadmill test (ETT)-induced myocardial ischaemia in subjects with stable CAD ( n = 23; age range: 53-75 years, all exhibited ST-segment depression > 1.5 mm at screening ETT at > 5METS). Haemodynamic responses to sublingual nitroglycerin (NTG) were assessed before and after ETT. ResultsCompared with placebo, tadalafil did not significantly affect the time to ETT-induced ischaemia (13 min/31 s vs. 13 min/36 s, respectively). Before exercise, NTG evoked decreases in sitting systolic blood pressure (SBP) that were significantly greater when subjects received tadalafil compared with placebo, and after exercise, more subjects experienced a decrease in SBP < 85 mmHg in response to NTG after taking tadalafil vs. placebo. When subjects received tadalafil compared with placebo, SBP was lower at rest ( -7 mmHg; -12,-2), during ETT ( -10 mmHg; -16, -3), and after ETT ( -13 mmHg; -19, -7). ConclusionTadalafil did not significantly alter the time to ETT-induced ischaemia compared with placebo in subjects with CAD. Tadalafil reduced resting and exercise SBP. Due to the potential for hypotension, the concomitant use of nitrates and tadalafil is contraindicated. D. Patterson et al. 46060 :5 Br J Clin Pharmacol