Cardiovascular actions of angiotensin-(1-12) in the hypothalamic paraventricular nucleus of the rat are mediated via angiotensin II

摘要

The role of hypothalamic paraventricular nucleus (PVN) in cardiovascular regulation is well established. In this study, it was hypothesized that the PVN may be one of the sites of cardiovascular actions of a new angiotensin, angiotensin-(1-12). Experiments were carried out in urethane-anaesthetized, artificially ventilated, adult male Wistar rats. PVN was identified by microinjections of N-methyl-D-aspartic acid (NMDA, 10 mM). Microinjections (50 nl) of angiotensin-(1-12) (1 mM) into the PVN elicited increases in mean arterial pressure (MAP), heart rate (HR) and renal nerve activity (RSNA). The tachycardic responses to angiotensin-(1-12) were attenuated by bilateral vagotomy. The cardiovascular responses elicited by angiotensin-(1-12) were attenuated by microinjections of an angiotensin II type 1 receptor (AT1R) antagonist (losartan), but not AT2R antagonist (PD123319), into the PVN. Combined inhibition of angiotensin converting enzyme (ACE) and chymase in the PVN abolished angiotensin-(1-12)-induced responses. Angiotensin-(1-12)-immunoreactive cells and fibres were more numerous in the middle and caudal regions of the PVN. Angiotensin-(1-12) was present in many, but not all, vasopressinergic PVN cells. This peptide was also present in some non-vasopressinergic PVN cells but not in oxytocin containing PVN cells. These results indicated that: 1) microinjections of angiotensin-(1-12) into the PVN elicited increases in MAP, HR, and RSNA, 2) HR responses were mediated via both sympathetic and vagus nerves, 3) both ACE and chymase were needed to convert angiotensin-(1-12) to angiotensin II in the PVN, and 4) AT1Rs, but not AT2Rs, in the PVN mediated angiotensin-(1-12)-induced responses. It was concluded that the cardiovascular actions of angiotensin-(1-12) in the PVN are mediated via its conversion to angiotensin II.