Effect of the AT1-Receptor Antagonists Losartan, Irbesartan, and Telmisartan on Angiotensin II-Induced Facilitation of Sympathetic Neurotransmission in the Rat Mesenteric Artery

SUMMARY: The effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II (Ang II)-induced facilitation of noradrenergic neurotransmission was investigated in the isolated rat mesenteric artery under isometric conditions. Electrical field stimulation (2, 4, and 8 Hz) caused a frequency-dependent increase of contractile force. At stimulation frequencies of 2, 4, and 8 Hz, Ang 11 (10 nM) increased the stimulation-induced vasoconstrictor responses by a factor 4.8 +/- 0.9, 2.9 +/- 0.7, and 1.3 +/- 0.1, respectively (p irbesartan > losartan (p < 0.05 between linear regression lines). Contractile responses to exogenous noradrenaline were unaltered in the presence of Ang II 10 nM. We conclude that the facilitating effect of Ang II on noradrenergic neurotransmission is mediated by presynaptically located AT1-receptors. Conversely, this facilitating effect can be dose-dependently counteracted by blockade of these receptors. Sympathoinhibitory properties are likely to contribute to the therapeutic effect of AT1-blockers, in particular in conditions in which the sympathetic nervous system is activated, such as congestive heart failure and hypertension.