Complex mechanisms responsible for the pressor response of angiotensin 1-7 injected into the rat paraventricular nucleus of the hypothalamus

Aims: In our previous experiments, we demonstrated, that acute injection of angiotensin 1-7 (Ang 1-7) into the paraventricular nucleus of the hypothalamus (PVN) increased blood pressure (BP) via activation of Mas receptors, higher in hypertensive than normotensive rats (Mińczuk et al., Cells. 2022;11:1542). The aim of our current study was to explore potential mechanism(s) of the pressor response of Ang 1-7 injected into the PVN. Methods: Respective antagonists and Ang 1-7 were injected into the PVN of urethane-anesthetized Wistar rats. Results: Injection of Ang 1-7 (0.3 nmol/rat) into the PVN raised BP by about 15 mmHg. This response was completely blocked by glutamatergic AMPA/kainite and NMDA receptor antagonists CNQX (0.2 nmol/rat) and D-AP5 (0.3 nmol/rat). In addition, it was reduced by about 70% in the presence of antagonists for GABAA and thromboxane A2 receptors, bicuculline (0.4 nmol/rat) and SQ29548 (10 nmol/rat), respectively, and even reversed by vasopressin V1A and V1B receptor antagonists conivaptan (16 nmol/rat) and nelivaptan (16 nmol/rat), respectively. Pressor response of Ang 1-7 was not modified by antagonists of α1-adrenergic (prazosin; 20 nmol/rat) and purinergic P2X (PPADS; 0.5 nmol/rat) receptors. Conclusions: Acute administration of Ang 1-7 into the PVN of urethane-anesthetized rats, raises BP via complex mechanisms involving not only Mas receptors but also glutamatergic receptors, as well as receptors for vasopressin, thromboxane A2 and GABAA.