Cross-Talk between CB1, AT1, AT2 and Mas Receptors Responsible for Blood Pressure Control in the Paraventricular Nucleus of Hypothalamus in Conscious Spontaneously Hypertensive Rats and Their Normotensive Controls

We have previously shown that in urethane-anaesthetized rats, intravenous injection of the angiotensin II (Ang II) AT(1) receptor antagonist losartan reversed the pressor effect of the cannabinoid CB1 receptor agonist CP55940 given in the paraventricular nucleus of hypothalamus (PVN). The aim of our study was to determine the potential interactions in the PVN between CB1 receptors and AT(1) and AT(2) receptors for Ang II and Mas receptors for Ang 1-7 in blood pressure regulation in conscious spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. The pressor effects of Ang II, Ang 1-7 and CP55940 microinjected into the PVN were stronger in SHRs than in WKYs. Increases in blood pressure in response to Ang II were strongly inhibited by antagonists of AT(1) (losartan), AT(2) (PD123319) and CB1 (AM251) receptors, to Ang 1-7 by a Mas antagonist (A-779) and AM251 and to CP55940 by losartan, PD123319 and A-779. Higher (AT(1) and CB1) and lower (AT(2) and Mas) receptor expression in the PVN of SHR compared to WKY may partially explain the above differences. In conclusion, blood pressure control in the PVN depends on the mutual interaction of CB1, AT(1), AT(2) and Mas receptors in conscious spontaneously hypertensive rats and their normotensive controls.