P239Human resistance artery relaxing responses to an angiotensin AT2 receptor agonist depend on the type of contractile stimulus

    loading  Checking for direct PDF access through Ovid


Aim: Test whether stimulation of angiotensin type 2 receptors (AT2R) reduces effects of various vasoconstrictor stimuli in resistance-sized arteries of cardiovascular disease patients.

Methods: From biopsies of the parietal pericardium, obtained during open cardio-thoracic surgeries and stored overnight in physiological salt solution (PSS), 4 arterial segments were micro dissected, mounted in wire myographs, and studied at a diameter (202 ± 6 μm) corresponding to a distending pressure of 100 mmHg. Relaxing responses were recorded during submaximal contractions and compared to appropriate "time controls".

Results: 10 μM acetylcholine reduced contractile responses to 32 mM K+, suggesting presence of functional endothelium. Angiotensin II (0.1 – 100 nM) caused transient contractions that could be prevented by 3 nM valsartan (AT1R antagonist) and that tended to be reduced by 10 μM PD123319 (AT2R antagonist). 24 mM K+, 0.1 μM U46619 (thromboxane A2 analogue) and 2 nM endothelin-1 (ET-1) caused submaximal contractions of comparable amplitude. Increasing concentrations of the AT2R agonist Compound 21 (C21, 0.1 – 100 nM) did not modify these contractile responses to K+ (n = 14) or ET-1 (n = 7). However, 100 nM C21 significantly reduced the contraction induced by U46619 by 53± 11 % (n = 9) and this relaxation was not influenced by valsartan.

Conclusion: A non-peptidergic AT2R agonist can relax intact pericardial resistance arteries of patients with ischemic heart disease and/or cardiac valve problems. This effect is either selective for mechanisms stimulated by thromboxane or inhibited by depolarization and ET-1, a potent stimulus of oxidative stress.

Related Topics

    loading  Loading Related Articles