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Abstract

Angiotensin II (Ang II) enhances sympathetic neurotransmission via AT₁-receptors located on sympathetic nerve terminals. We recently demonstrated that inhibition of Ang II-mediated facilitation in the pithed rat by irbesartan resulted in a U-shaped dose response curve, which was not observed when PD 123319, at a concentration that selectively blocks the AT₂-receptor, was co-administered. Hence, the irbesartan-mediated `upstroke' might be explained by the involvement of the AT₂-receptor after AT₁ blockade with high-dose irbesartan. In the present study, we further investigated the possible role of the AT₂-receptor in Ang II-mediated facilitation in vitro.

We studied the effect of the AT₂-receptor antagonist PD 123319 (10 nM) on Ang II-enhanced sympathetic outflow evoked by electrical field stimulation (EFS) in the rat isolated inferior vena cava. Additionally, we investigated the effect of the AT₁-receptor blocker irbesartan (0.1 nM—1 µM) on the sequelae of Ang II-enhanced, EFS-evoked sympathetic nerve traffic in the presence or absence of PD 123319 (10 nM).

PD 123319 did not influence Ang II-enhanced sympathetic outflow. Irbesartan dose-dependently attenuate Ang II-augmented transmitter release (pIC₅₀ 7.99±0.03), whereas no U-shaped concentrationresponse relationship for irbesartan was observed. Co-administration of PD 123319 with irbesartan proved unable to influence Ang II-mediated facilitation differently compared with irbesartan alone. The experimental observations indicate that the AT₂-receptor is not involved in Ang II-mediated enhancement of sympathetic nerve traffic in the present in vitro study.

Keywords

angiotensin II AT1-receptor AT2-receptor irbesartan PD 123319 cardiovascular

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No involvement of the AT2-receptor in angiotensin II-enhanced sympathetic transmission in vitro

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