Evidence for functional expression of vascular angiotensin II type 2 receptors in patients with insulin resistance

Aim: Angiotensin II type 2 (AT2) receptors are believed to become over-expressed in response to cardiovascular damage and to mediate beneficial effects (e.g. vasodilation). It is unknown whether AT2 receptors are functionally expressed in patients with insulin resistance (INSR). In this study, we investigated the role of the highly selective AT2 receptor antagonist, PD123319, on arterial stiffness and haemodynamic parameters in patients with INSR, compared with an age- and gender-matched control (N) group to determine whether there is functional expression of vascular AT2 receptors in patients with INSR. Methods: We studied 10 subjects with INSR [mean age 28 +/- 5 years, body mass index (BMI) 30.4 +/- 5.4 kg/m(2), mean cholesterol level 4.7 +/- 0.7 mmol/l, mean homeostasis model assessment 2.78 +/- 0.84] and 10 age- and gender-matched normal subjects (mean age 27 +/- 7 years, BMI 23.6 +/- 2.5 kg/m(2), mean cholesterol level 3.9 +/- 0.6 mmol/l). All were normotensive, non-smokers and on no medications. Subjects received a 3-min infusion of PD123319 (10 mu g/min). At the end of the infusion, arterial stiffness indices [stiffness index (SI) and reflective index (RI)] and haemodynamic parameters [cardiac index, systemic vascular resistance index (SVRI) and stroke index (ZI)] were measured. Results: RI (mean % change: INSR 13.8 +/- 15.5%, N -0.2 +/- 4.6, p = 0.04) and SVRI (mean % change: INSR 13.5 +/- 9.7%, N -1.5 +/- 5.7, p = 0.005) increased significantly in response to PD123319 infusion in patients with INSR compared with controls. There were no significant changes in SI, systolic blood pressure, diastolic blood pressure and ZI. Conclusion: The results suggest the functional expression of AT2 receptors in small vessels that determine the inflection of the digital volume pulse wave in patients with INSR, possibly as an indicator of early vascular damage.