Cardiovascular effect of angiotensin-(1–12) in the caudal ventrolateral medullary depressor area of the rat

Abstract

Angiotensin (ANG)-(1–12) excites neurons via ANG II type 1 receptors (AT1Rs), which are present in the caudal ventrolateral medullary depressor area (CVLM). We hypothesized that microinjections of ANG-(1–12) into the CVLM may elicit decreases in mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity. This hypothesis was tested in urethane-anesthetized adult male Wistar rats. Microinjections of ANG-(1–12) into the CVLM elicited decreases in MAP, HR, and greater splanchnic nerve activity (GSNA). ANG-(1–12)-induced responses consisted of initial (first 1–8 min) and delayed (8–24 min) phases. Prior microinjections of losartan, A-779, and captopril into the CVLM blocked initial, delayed, and both phases of ANG-(1–12) responses, respectively. Blockade of GABA receptors in the rostral ventrolateral medullary pressor area (RVLM) attenuated cardiovascular responses elicited by microinjections of ANG-(1–12) into the ipsilateral CVLM. Microinjections of ANG-(1–12) into the CVLM potentiated the reflex decreases and attenuated the reflex increases in GSNA elicited by intravenous injections of phenylephrine and sodium nitroprusside, respectively. These results indicate that microinjections of ANG-(1–12) into the CVLM elicit decreases in MAP, HR, and GSNA. Initial and delayed phases of these responses are mediated via ANG II and ANG-(1–7), respectively; the effects of ANG II and ANG-(1–7) are mediated via AT1Rs and Mas receptors, respectively. Captopril blocked both phases of ANG-(1–12) responses, indicating that angiotensin-converting enzyme is important in mediating these responses. GABA receptors in the RVLM partly mediate the cardiovascular responses to microinjections of ANG-(1–12) into the CVLM. Microinjections of ANG-(1–12) into the CVLM modulate baroreflex responses.