Increase in systemic blood pressure during intra-arterial PD123319 infusion: evidence for functional expression of angiotensin type 2 receptors in normal volunteers.

The functional existence of angiotensin type 2 (AT2) receptors in healthy humans is uncertain. A double-blind, randomized, crossover study was performed comparing forearm vascular responses to intrabrachial arterial PD123319 (a selective AT2 receptor antagonist, 10 microg/min) in healthy young, non-smoking volunteers following 1 week of telmisartan therapy (40-80 mg once daily) and 1 week of placebo therapy. No significant difference was found in baseline mean arterial pressure between telmisartan and placebo treatment. Baseline forearm blood flow (FBF) was significantly higher during telmisartan (2.69 +/- 1.28 ml/s) therapy than during placebo (1.86 +/- 0.75 ml/s). PD123319 did not alter FBF on either telmisartan or placebo therapy. However, significant increases in mean arterial pressure were observed during intra-brachial arterial infusions of PD123319 (p=0.003) during both placebo (80 +/- 9 to 92 +/- 17 mmHg) and telmisartan (80 +/- 11 to 90 +/- 14 mmHg) therapy suggesting the presence of functional AT2 receptors, possibly in locations other than the forearm resistance vessels. Intra-brachial arterial infusion of PD123319 (10 microg/min) has significant systemic effects, which appear more prominent than local changes in FBF and which are not influenced by angiotensin type 1 receptor blockade.