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

Abstract

The role of the 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 newly discovered angiotensin, angiotensin-(1-12). Experiments were carried out in urethane-anaesthetized, artificially ventilated, adult male Wistar rats. The PVN was identified by microinjections of NMDA (10 mm). Microinjections (50 nl) of angiotensin-(1-12) (1 mm) into the PVN elicited increases in mean arterial pressure, heart rate and renal sympathetic nerve activity. 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 an angiotensin II type 1 receptor (AT2R) antagonist (PD123319), into the PVN. Combined inhibition of angiotensin-converting enzyme 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 can be summarized as follows: (1) microinjections of angiotensin-(1-12) into the PVN elicited increases in mean arterial pressure, heart rate and renal sympathetic nerve activity; (2) heart rate responses were mediated via both sympathetic and vagus nerves; (3) both angiotensin-converting enzyme 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. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society.