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.

IntroductionThis study investigated the central haemodynamic, blood pressure (BP) and pulse wave responses to progressively increasing infusion rates of intravenous angiotensin II (Ang II) in normal volunteers during chronic therapy with telmisartan or placebo. Materials and methodsTen normal volunteers, aged 21-33 years, completed a ramdomised, double-blind crossover study. Ang II was infused intravenously at increasing infusion rates (0-512 ng/minute) at the end of one week of telmisartan therapy (40-80 mg/day) and one week of placebo therapy. BP, central haemodynamics and pulse wave parameters were monitored continuously using a CardioDynamics Recorder, a Pulse Tracer Recorder and a Finipress Recorder. ResultsBaseline diastolic BP (57+12 vs. 67+13 mmHg) and pulse wave reflection index (RI) (38.4+18.6 vs. 60.6+12.5%) were significantly lower on telmisartan than on placebo therapy. Cardiac index (CI), systolic BP, systemic vascular resistance index (SVRI), RI and pulse wave stiffness index (SI) were all significantly increased in a dose-dependent manner by Ang II on placebo therapy. Telmisartan significantly (p<0.05) attenuated all of these responses to Ang II. Increases in BP during Ang II infusion were associated with increases in SVRI and CI. ConclusionsTelmisartan effectively blocked the effects of intravenous Ang II on CI, BP, RI and SI in healthy volunteers. Changes in CI make a major contribution to increase in BP response to intravenous Ang II in normal volunteers. IntroductionAngiotensin receptor blockers (ARBs) reduce blood pressure (BP) by reducing systemic vascular resistance index (SVRI) while leaving cardiac index (CI) essentially unchanged.