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 be 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 of 12.8 +/- 0.6 mmHg (P < 0.0005), and 16.2 +/- 1.4 mmHg (P < 0.0001) respectively, without effect on heart rate. These responses were significantly attenuated following systemic administration of losartan, an ANG type 1 receptor (AT1) antagonist (Control, +12.8 +/- 0.6 mmHg; post-losartan, +5.6 +/- 1.7 mmHg), but were unaffected by the AT2 receptor antagonist, PD123319 (Control, +10.8 +/- 1.6 mmHg; post-PD123319, +11.6 +/- 2.4 mmHg). Initial and later components of the biphasic pressor response elicited by electrical stimulation of SFO (200 microA, 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 was 16.6 +/- 2.3 mmHg in comparison to a post-losartan increase of 9.3 +/- 1.6 mmHg (P < 0.001). Similarly, the secondary response consisted of a control increase of 9.6 +/- 1.3 mmHg and a post-losartan increase of 3.4 +/- 0.9 mmHg (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)