Effects of intravenous PD 123319 on haemodynamic and arterial stiffness indices in healthy volunteers

Relatively little is known about the functional expression of cardiovascular angiotensin type 2 (AT(2))-receptors in healthy young adult humans. We performed a randomised, placebo-controlled crossover study of the effects of intravenous administration of the selective AT(2)-receptor antagonist PD 123319 on haemodynamics and arterial stiffness in normal volunteers. Sixteen normal subjects aged 29.9 +/- 13.8 years (range 18-30 years) received an intravenous infusion of PD 123319 (10 mcg/minute for 5 minutes) and placebo, separated by one week. Haemodynamics (cardiac index, stroke index and systemic vascular resistance) were measured non-invasively using a BioZ.com thoracic impedance detection system. Blood pressure was measured from an arm cuff using oscillometry. Stiffness index, a measure of arterial stiffness, was measured using a PulseTrace recorder. No significant changes in blood pressure (P=0.92), cardiac index (p=0.52), stroke index (p=0.61), systemic vascular resistance index (p=0.32) or stiffness index (p=0.57) was demonstrated following PD 123319 infusion, compared with placebo. The results of this study do not support the functional presence of cardiovascular AT(2)-receptors that mediate acute haemodynamic effects in healthy young adults. It remains possible that higher doses of PD 123319 may be required to demonstrate functional cardiovascular AT(2)-receptors in this population, if they are present.