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Effects of Intravenous PD 123319 on Haemodynamic and Arterial Stiffness Indices in Healthy Volunteers

Department of Medicine St. George Clinical School, University of New South Wales, Kogarah NSW 2217 Australia

Martina T Johnstone

Department of Nuclear Medicine, St. George Hospital, Kogarah NSW 2217 Australia

Laurence G Howes

Department of Pharmacology and Therapeutics Gold Coast Hospital, Griffith University, Southport, QLD 4215 5 Australia, laurie_howes{at}health.qld.gov.au

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 AT₂-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 AT₂receptors 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 AT₂-receptors in this population, if they are present.

Key Words: PD 123319 • AT2-receptor • Arterial stiffness • Blood pressure • Haemodynamics

Journal of Renin-Angiotensin-Aldosterone System, Vol. 6, No. 2, 102-106 (2005)
DOI: 10.3317/jraas.2005.007


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