Angiotensin II actions in paraventricular nucleus: functional evidence for neurotransmitter role in efferents originating in subfornical organ

Abstract

Angiotensin II (ANG) has been suggested to be the neurotransmitter utilised by subfornical organ (SFO) efferents projecting to the paraventricular nucleus (PVN). The PVN has been shown to been involved in mediating the cardiovascular response elicited by electrical stimulation of SFO. The possible role of ANG as a neurotransmitter in these pathways has been examined in the present study. The cardiovascular effects of ANG microinjection into the PVN were examined in urethane anaesthetized, male Sprague-Dawley rats. Microinjection of 20 ng or 50 ng ANG into PVN resulted in mean increases in blood pressure of12.8±0.6mmHg ( P < 0.0005), and16.2±1.4mmHg ( P < 0.0001) respectively, without effect on heart rate. These responses were significantly attenuated following systemic administration of losartan, an ANG type 1 receptor (AT 1) antagonist (Control,+12.8±0.6mmHg; post-losartan,+ 5.6±1.7mmHg), but were unaffected by the AT 2 receptor antagonist, PD123319 (Control,+ 10.8±1.6 mmHg; post-PD12319,+ 11.6±2.4 mmHg). Initial and later components of the biphasic pressor response elicited by electrical stimulation of SFO (200 μA, 10 Hz, 1 ms pulse width, 10 s) were also significantly attenuated by losartan, but unaffected by PD123319. The short latency increase in mean arterial pressure was16.6±2.3mmHg in comparison to a post-losartan increase of9.3±1.6 mmHg ( P < 0.001). Similarly, the secondary response consisted of a control increase of9.6±1.3mmHg and a post-losartan increase of3.4±0.9 mmHg ( P < 0.001). In contrast, neither the initial (control response of+ 15.6±1.5mmHg and post-PD123319 response of15.2±1.3 mmHg ( P > 0.5), nor the secondary response (+6.0±1.0 mmHg control value and a post-PD123319 value of+6.3±1.3 mmHg ( P > 0.8), were affected by administration of PD123319. These findings demonstrate that ANG elicits pressor effects when microinjected into PVN through actions mediated by the AT 1 receptor, and support the hypothesis that ANG may be utilised as a neurotransmitter by efferents originating in SFO.