Angiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors.

Although angiotensin 1-7 (Ang 1-7) and its role as a part of the "protective" axis of the renin-angiotensin system are well described in the literature, the mechanisms of its angiotensin II-like pressor and tachycardic effects following its acute central administration are not fully understood. It was the aim of the present study to examine which receptors contribute to the aforementioned cardiovascular effects. Ang 1-7 and antagonists for glutamate, GABA, vasopressin, thromboxane A₂ (TP), α₁-adrenergic, and P2X purinoceptors or modulators of oxidative stress were injected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anesthetized male Wistar rats. Acute injection of Ang 1-7 into the PVN increased blood pressure (BP) by about 15 mmHg and heart rate (HR) by about 14 beats/min. After preinjection with bicuculline (GABA_A receptor antagonist), CNQX + D-AP5 (AMPA/kainate and NMDA receptor antagonists) and SQ29548 (TP receptor antagonist) the BP and HR reactions to Ang 1-7 were attenuated or abolished. The vasopressin V_1A and V_1B receptor antagonists conivaptan and nelivaptan, and the NADPH oxidase inhibitor apocynin even reversed the pressor and tachycardic effects of Ang 1-7. Antagonists of P2X (PPADS) and α₁-adrenergic receptors (prazosin), the free radical scavenger tempol and the superoxide dismutase inhibitor DETC did not modify the cardiovascular effects of Ang 1-7. The (Mas receptor-related) rise in BP and HR evoked by Ang 1-7 administered to the rat PVN is linked to glutamate, vasopressin, GABA_A and thromboxane receptors, and to oxidative stress, but does not seem to involve α₁-adrenergic or P2X receptors.