Inhibition of angiotensin II-induced facilitation of sympathetic neurotransmission in the pithed rat: a comparison between losartan, irbesartan, telmisartan and captopril

Objective Numerous studies have shown that angiotensin II enhances sympathetic nervous transmission. The objective of the present study was to quantify the inhibitory effect of the angiotensin II type 1 (AT(1)) receptor blockers losartan, irbesartan and telmisartan and the angiotensin converting enzyme (ACE) inhibitor captopril on sympathetic neurotransmission and to compare the potency of these agents both at the presynaptic and the postsynaptic levels, Design In the male, normotensive pithed rat model, we studied the effect of losartan (1,3, 10 and 30 mg/kg), irbesartan (3, 10, 30 and 60 mg/kg), telmisartan (0.3, 1,3 and 10 mg/kg) and captopril(1.5, 5, 15 and 45 mg/kg) on electrical stimulation of the thoraco-lumbar spinal cord. To investigate the interaction between postsynaptic AT(1) receptors and a-adrenoceptors, the effects of these compounds on presser responses to exogenous noradrenaline were studied, Results Stimulation of the thoracolumbar spinal cord caused a stimulation-frequency dependent rise in diastolic blood pressure (DBP) that could be dose-dependently reduced by both AT(1) receptor blockade and ACE inhibition. Interestingly, the highest doses of the AT(1) antagonists caused less than maximal reduction in the rise in DBP. This phenomenon was not observed after ACE inhibition by captopril. In experiments with exogenous noradrenaline, no effect of AT(1) blockade or ACE inhibition on alpha -adrenoceptor-mediated blood pressure responses was seen. Conclusion We conclude that, in the pithed rat model, the effects of stimulation of the thoraco-lumbar spinal cord on DBP are counteracted by blockade of presynaptically located AT(1) receptors, The order of potency concerning sympatico-inhibition is telmisartan > losartan > irbesartan. Regarding the inhibition of angiotensin II-induced facilitation of sympathetic neurotransmission, marked differences were observed between selective AT(1) blockade and ACE inhibition, The finding that all three AT(1) blockers cause less than maximal inhibition in their highest doses, as opposed to captopril, suggests that this is a class effect of the AT(1) antagonists, I Hypertens 19:465-473 (C) 2001 Lippincott Williams & Wilkins.