Angiotensin‐(1–12) in the rostral ventrolateral medullary pressor area of the rat elicits sympathoexcitatory responses

New Findings What is the central question of this study? Although brain angiotensin‐(1–12), a new member of the RAS, levels are significantly higher than angiotensin II very little information is available on its mechanism of central actions. What is the main finding and its importance? This study provides evidence that both ACE and chymase‐mediated conversion of angiotensin‐(1–12) to angiotensin II are key in its cardiovascular actions involving angiotensin II type 1 and not type 2 receptors. The rostral ventrolateral medullary pressor area (RVLM) is known to be critical in the regulation of cardiovascular function. In this study, it was hypothesized that the RVLM may be one of the sites of cardiovascular actions of a newly discovered angiotensin, angiotensin‐(1–12) [Ang‐(1–12)]. Experiments were carried out in urethane‐anaesthetized, artificially ventilated, adult male Wistar rats. The RVLM was identified by microinjections of l ‐glutamate (5 m m ). The volume of all microinjections into the RVLM was 100 nl. Microinjections of Ang‐(1–12) (0.1–1.0 m m ) into the RVLM elicited increases in mean arterial pressure and heart rate. Maximal cardiovascular responses were elicited by 0.5 m m Ang‐(1–12); this concentration was used in the other experiments described. Microinjections of Ang‐(1–12) increased greater splanchnic nerve activity. The tachycardic responses to Ang‐(1–12) were not altered by bilateral vagotomy. The cardiovascular responses elicited by Ang‐(1–12) were attenuated by microinjections of an angiotensin II type 1 receptor (AT 1 R) antagonist (losartan), but not an AT 2 R antagonist (PD123319), into the RVLM. Combined inhibition of angiotensin‐converting enzyme and chymase in the RVLM abolished Ang‐(1–12)‐induced responses. Angiotensin‐(1–12)‐immunoreactive cells were present in the RVLM. Angiotensin II type 1 receptors and phenylethanolamine‐ N ‐methyl‐transferase were present in the RVLM neurons retrogradely labelled by microinjections of Fluoro‐Gold into the intermediolateral cell column of the thoracic spinal cord. Angiotensin‐(1–12)‐containing neurons in the hypothalamic paraventricular nucleus did not project to the RVLM. These results indicated that: (1) microinjections of Ang‐(1–12) into the RVLM elicited increases in mean arterial pressure, heart rate and greater splanchnic nerve activity; (2) both angiotensin‐converting enzyme and chymase were needed to convert Ang‐(1–12) into angiotensin II; and (3) AT 1 Rs, but not AT 2 Rs, in the RVLM mediated the Ang‐(1–12)‐induced responses.