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.
Gilles
Rozemarie
R
Department of Clinical Pharmacology, St George Hospital, UNSW, Kogarah NSW 2217, Australia.
Vingerhoedt
Noreen
N
Howes
Jan
J
Griffin
Matthew
M
Howes
Laurence Guy
LG
D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D057912:Angiotensin II Type 2 Receptor Blockers; D001562:Benzimidazoles / Q000008:administration & dosage; D001565:Benzoates / Q000008:administration & dosage; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D005260:Female; D005542:Forearm; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007261:Infusions, Intra-Arterial; D008297:Male; D011725:Pyridines / Q000008:administration & dosage*; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D000077333:Telmisartan; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; C073402:PD 123319; D000077333:Telmisartan