Haemorrhage increases the pressor effect of angiotensin-(1–7) but not of angiotensin II at the rat rostral ventrolateral medulla

OBJECTIVETo evaluate the effects of angiotensins acting at the rostral ventrolateral medulla (RVLM) on the cardiovascular adjustments following haemorrhage. DESIGNChanges in mean arterial pressure (MAP) and heart rate (HR) produced by micro-injections of angiotensin II (Ang II) and angiotensin (Ang)-(1–7) and different angiotensin antagonists into the RVLM of anaesthetized rats submitted to haemorrhage, were determined. METHODSExperiments were performed in 79 urethaneanaesthetized male Wistar rats. Ang-(1–7) (2.5 and 25 pmol), Ang II (25 pmol), [Sar, Thr]-Ang II (non-selective angiotensin antagonist, 0.2 nmol), A-779 (Ang-(1–7) antagonist, 0.1 nmol), losartan (AT1 Ang II receptor antagonist, 0.2 nmol) or vehicle (200 nl) were bilaterally micro-injected into the RVLM under basal conditions or 30 min after blood withdrawal (0.6 ml/100 g bodyweight). In additional groups, [Sar, Thr]-Ang II, A-779, losartan or vehicle were micro-injected into the RVLM 10 min before bleeding to uncover a possible role of endogenous peptides during haemorrhage. RESULTSThe pressor effect produced by Ang II microinjection was not altered by haemorrhage. Conversely, haemorrhage significantly increased the magnitude and duration of the pressor effect of Ang-(1–7) at the RVLM. The fall in MAP induced by haemorrhage was similar after micro-injection of vehicle or A-779. However, microinjection of [Sar, Thr]-Ang II significantly reduced the fall in MAP after haemorrhage. A similar finding was obtained with micro-injection of losartan. In addition, while RVLM micro-injection of [Sar, Thr]-Ang II or losartan 30 min after blood withdrawn produced MAP changes that were similar to that observed in control animals, micro-injection of A-779 did not significantly alter baseline MAP. CONCLUSIONSThese results suggest that changes in the RVLM reactivity to Ang-(1–7) but not Ang II may contribute to the haemodynamic adjustments triggered by acute reductions in blood volume. The data obtained with [Sar, Thr]-Ang II and losartan suggest a primary inhibitory role for endogenous Ang II at the RVLM during haemorrhage.