Effects of Angiotensin Ii on the Medullaryneurons and Their Sensitivity to Acetylcholine and Catecholamines

Abstract

Abstract-In order to elucidate the mechanism of the central hypertensive action of angiotensin II (ATzi), the effects of ATII on the medullary neurons of rabbits were studied by the technique of electrophoretic application.ATII gave rise to excitatory effect on some neurons of medulla and this effect was antagonized by a specific AT,, antagonist, 1-sarcosine-8-alanine-ATi1.The ATII sensitive medullary neurons showed no specific response to acetylcholine, norepinephrine or isoproterenol, but there was a significant increase in the excitatory response to norepinephrine in comparison with the ATrr non-sensitive neurons. The excitatory effect of AT,, was not blocked by atropine, phentolamine and propranolol.The ATII sensitive neurons in the medulla apparently do not have a topograhically or functionally characteristic distribution related to the central vasomotor control mechanisms. The neurons in the area postrema did not respond to electrophoretically applied ATII, while microinjection of ATII in this region produced remarkable hypertensive responses. These results suggest that the mechanism of the central hypertensive action of ATI i administered into the vertebral artery is primarily mediated by the chemoreception of the area postrema. The mecha nism of central cardiovascular effect of ATrr and of the effects of acetylcholine and catecholamines on the medullary neurons are discussed.Since the first observation of a central effect of angiotensin II (AT,,) in dogs (1), con siderable evidence has accumulated that at least some of the hypertensive effects of AT,, are mediated by an action on the central mechanisms of the autonomic nervous system (2).The lower medulla is considered by several investigators to be one of the sites of central

Brain renin–angiotensin system dysfunction in hypertension: recent advances and perspectives

“…These effects are mediated by the AT 1 receptor as they occur in the presence of an AT 2 receptor antagonist and are abolished by losartan, an AT 1 receptor antagonist. These effects are consistent with the effects of Ang II on I A and neuronal firing in SFO, PVN and SON neurons as well as on neuronal firing rate in MnPO and RVLM neurons in brain slices or in situ (Felix & Schlegel, 1978; Suga & Suzuki, 1979; Tasker & Dudek, 1991; Yang et al ., 1992; Armstrong, 1995; Ferguson & Li, 1996; Li & Ferguson, 1996; Bai & Renaud, 1998). PKC inhibition attenuates Ang II‐induced decreases in I A and I Kv and abolishes Ang II‐evoked increases in total Ca 2+ current, indicating that Ang II effects on these ion channel currents are either partly or wholly mediated by PKC (Sumners et al ., 1996; Wang et al ., 1997; Zhu et al ., 1999).…”

Angiotensin At1Receptor Signalling Pathways In Neurons

“…For example, AngII elicits an AT 1 receptor‐mediated decrease in I A in neurons from the subfornical organ (SFO), supraoptic nucleus and paraventricular nucleus (PVN) magnocellular area contained in brain slices 31–33 . In addition, selective activation of neuronal AT 1 receptors in situ or in brain slices increases the firing rate of neurons in specific brain regions, such as the SFO, PVN and rostral ventrolateral medulla (RVLM) 34–37 …”

Angiotensin II increases respiratory rhythmic activity in the preBötzinger complex without inducing astroglial calcium signaling

“…Injection of Ang II into the nucleus of the solitary tract, which relays CB input to other brainstem respiratory control regions, was shown to increase the respiratory rate in rats ( Paton and Kasparov, 1999 ). Furthermore, Ang II signaling via its main receptor, the angiotensin II type 1 receptor (AT1R), increases the firing rate of neurons in brain areas involved in controlling the cardiovascular system, including the subfornical organ (SFO), paraventricular nucleus of the hypothalamus (PVN), organum vasculosum of the lamina terminalis (OVLT) ( Felix and Schlegel, 1978 ; Suga et al, 1979 ; Knowles and Phillips, 1980 ; Harding and Felix, 1987 ; Cancelliere and Ferguson, 2017 ) and the RVLM ( Chan et al, 1991 ; Matsuura et al, 2002 ; Dampney et al, 2007 ). The PVN and SFO also regulate respiration ( Ferguson et al, 1989 ; Yeh et al, 1997 ).…”