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

Objective To evaluate the effects of angiotensins acting at the rostral ven trolateral medulla (RVLM) on the cardiovascular adjustments following haemo rrhage. Design Changes 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 s ubmitted to haemorrhage, were determined. Methods Experiments were performed in 79 urethane-anaesthetized male Wistar rats. Ang-(1-7) (2.5 and 25 pmol), Ang II (25 pmol), [Sar(1), Thr(8)]-Ang II (nonselective angiotensin antagonist, 0.2 nmol), A-779 (Ang-(1-7) antago nist, 0.1 nmol), losartan (AT(1) Ang II receptor antagonist, 0.2 nmol) or v ehicle (200 nl) were bilaterally micro-injected into the RVLM under basal c onditions or 30 min after blood withdrawal (0.6 ml/100 g bodyweight). In ad ditional groups, [Sar(1), Thr(8)]-Ang II, A-779, losartan or vehicle were m icro-injected into the RVLM 10 min before bleeding to uncover a possible ro le of endogenous peptides during haemorrhage. Results The presser effect produced by Ang II microinjection was not altere d by haemorrhage. Conversely, haemorrhage significantly increased the magni tude and duration of the presser 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(1), Thr(8)]-Ang II significantly reduced the fall in MAP after haemorrhage. A similar finding was obtained w ith micro-injection of losartan, In addition, while RVLM micro-injection of [Sar(1), Thr(8)]-Ang II or losartan 30 min after blood withdrawn produced MAP changes that were similar to that observed in control animals, micro-in jection of A-779 did not significantly alter baseline MAP. Conclusions These results suggest that changes in the RVLM reactivity to An g-(1 - 7) but not Ang II may contribute to the haemodynamic adjustments tri ggered by acute reductions in blood volume. The data obtained with [Sar(1), Thr(8)]-Ang II and losartan suggest a primary inhibitory role for endogenou s Ang II at the RVLM during haemorrhage. J Hypertens 1999, 17:1145-1152 (C) Lippincott Williams & Wilkins.