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

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.

The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1–12) and angiotensin II

The hypothalamic arcuate nucleus (ARCN) has been reported to play a significant role in cardiovascular regulation. It has been hypothesized that the ARCN may be one of the sites of cardiovascular actions of angiotensins (ANGs). Experiments were carried out in urethane-anesthetized, artificially ventilated, adult male Wistar rats. The ARCN was identified by microinjections of N-methyl-d-aspartic acid (NMDA; 10 mM). Microinjections (50 nl) of ANG-(1–12) (1 mM) into the ARCN elicited increases in mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA). The tachycardic responses to ANG-(1–12) were attenuated by bilateral vagotomy. The cardiovascular responses elicited by ANG-(1–12) were attenuated by microinjections of ANG II type 1 receptor (AT1R) antagonists but not ANG type 2 receptor (AT2R) antagonist. Combined inhibition of ANG-converting enzyme (ACE) and chymase in the ARCN abolished ANG-(1–12)-induced responses. Microinjections of ANG II (1 mM) into the ARCN also increased MAP and HR. Inhibition of ARCN by microinjections of muscimol (1 mM) attenuated the pressor and tachycardic responses to intravenously administered ANG-(1–12) and ANG II (300 pmol/kg each). These results indicated that 1) microinjections of ANG-(1–12) into the ARCN elicited increases in MAP, HR, and GSNA; 2) HR responses were mediated via both sympathetic and vagus nerves; 3) AT1Rs, but not AT2Rs, in the ARCN mediated ANG-(1–12)-induced responses; 4) both ACE and chymase were needed to convert ANG-(1–12) to ANG II in the ARCN; and 5) ARCN plays a role in mediating the cardiovascular responses to circulating ANGs.