Angiotensin 1‐7 Receptor and Angiotensin II Receptor 2 Blockades Prevent the Increased Serum and Kidney Nitric Oxide Levels in Response to Angiotensin II Administration: Gender‐Related Difference

The angiotensin II (Ang II) receptor 2 (AT2R) and angiotensin 1‑7 receptor (masR) expression in the kidney are gender‑related. We attempted to compare the response of nitric oxide (NO) production to Ang II administration, with and without AT2R and masR blockades, using A‑779 and PD123319 in male and female rats. Anesthetized and catheterized male and female Wistar rats were subjected to one‑hour continuous infusion of Ang II (~20 μg/kg/hour), with and without masR and AT2R blockades. The level of the NO metabolite (nitrite) was measured before and after the experiment in rat serum and in the homogenized kidney tissue. The basal data indicated that no sex difference in the serum level of nitrite could be detected before Ang II infusion. However, administration of Ang II in male and female rats caused a gender difference in the nitrite level, which resulted in the serum level of the nitrite significantly increasing in males (P < 0.05) when compared with the females. In addition, masR blockade or co‑blockade of masR and AT2R in male rats abolished the gender difference related to the effect of Ang II on nitrite production. In the presence of masR and AT2R, or when masR alone was blocked, the level of nitrite in the kidney, in response to the Ang II infusion was not significantly different between the two sexes. On the contrary, masR and AT2R co‑blockades significantly decreased the kidney nitrite concentration response to Ang II administration in both male and female rats (P < 0.05), but no sex difference was detected. The renal vasculature of male rats may provide more response to Ang II administration‑induced NO, which is dependent on masR and AT2R. During dual masR + AT2R blockades, the kidney NO formation wasreduced in a non‑gender related manner.