An Ultrastructural Analysis of the Distribution of Angiotensin II in the Rat Brain

Abstract

Abstractlmmunopositive angiotensin I1 nerve fibres and terminals are widely distributed throughout the rat brain, including areas of the brain with and without a blood-brain barrier. Ultrastructural examination indicates that in the circumventricular organs (areas which lack a blood-brain barrier), many angiotensin Il-positive nerve terminals are closely aligned with fenestrated blood vessels and do not have synaptic specializations. This appearance is in contrast to that of angiotensin II terminals in regions with a blood-brain barrier where there exists a more typical synaptic configuration. In both cases, angiotensin II is contained within large (100 to 125 nm) vesicles which coexist with smaller, lucent, non-immunoreactive vesicles. These observations suggest a possible duality of function such that angiotensin II in circumventricular organs may be secreted into the circulation, whereas angiotensin I I in the remainder of the brain is more likely to be acting as a neurotransmitter or neuromodulator.The octapeptide, angiotensin 11 (ANG II), when administered into the CNS, causes a number of well-defined physiological and behavioural responses including thirst, vasopressin secretion, natriuresis, increased blood pressure and salt appetite (1-3).One of the major questions central to understanding the actions of ANG I1 in the brain has been the source of its production. Ganten et al. (4) isolated angiotensin I and A N G II from the rat brain and demonstrated the central nature of ANG I1 production by the intracerebroventricular administration of an inhibitor of angiotensin-converting enzyme which caused a reduction in local ANG 11. Furthermore, the presence of each of the components of the renin angiotensin system (RAS) has been demonstrated immunocytochemically (5-8) and the likelihood of local production supported by the identification of mRNA for renin and angiotensinogen (9, 10). However, the cellular disposition of each of the components of the RAS still remains unclear, as does the nature of their interaction and the degree of their anatomical overlap. Immunocytochemically-identified A N G I1 is contained in a network of neural pathways connecting areas of the forebrain and brainstem which are largely concerned with autonomic or homeostatic functions (11). It is on the basis of these studies and the good correlation of A N G 11-positive terminal fields with A N G II receptors (12-15) that ANG I1 is suggested to act as a neurotransmitter/neuromodulator in the CNS.The present study has sought to further elucidate the action of ANG 11 in the CNS by examining its ultrastructural distribution. In particular, we have focused on the nature of morphological interactions between A N G 11-positive elements and other neural and non-neural structures in a range of brain areas.Previous studies at the light microscopic (LM) level have shown ANG 11-positive structures, presumed to be terminals, to be aggregated both in circumventricular organs (CVOs) and in regions behind the blood-brain barrier. Because the function of ...

Brain Angiotensin and Body Fluid Homeostasis.

“…Immunohistochemical studies [6,7], which used antisera that did not distinguish between angiotensin II and angiotensin III, show that the sites in the brain containing the greatest number of angiotensin-containing neurons are the hypothalamic paraventricular (PVN) and supraoptic nuclei, the subfornical organ, the nucleus of the solitary tract, and periventricular regions. Several angiotensin-containing fiber pathways have been identified, the most prominent being bundles of longitudinally directed axons in the periventricular fiber system and medial forebrain bundle.…”

“…Furthermore, angiotensin-like immunoreactivity has been localized to neurosecretory vesicles in nerve terminalis. These were found in the vicinity of the perivascular spaces surrounding fenestrated blood vessels in circumventricular organs such as the median eminence and subfornical organ [7,8].…”

Central Mineralocorticoid Receptors and the Role of Angiotensin II and Glutamate in the Paraventricular Nucleus of Rats With Angiotensin II–Induced Hypertension

“…Regions in the circumventricular organs of the LT, that is, SFO and organum vasculosum of the LT known to project to parvocellular subdivisions of the PVN 22,23 are densely filled with Ang II-containing neurons. 24 Connections between the SFO and PVN seem to use Ang II as a neurotransmitter because stimulation of neurons in the SFO by Ang II increased Ang II release in the PVN. 25 Microinjection of Ang II in the SFO increased BP, and this effect of Ang II was prevented by an AT 1 -receptor blocker in the PVN.…”

Increased Angiotensin-(1–7) in Hypophysial-Portal Plasma of Conscious Sheep

“…Ang-( 1-7) is equipotent to Ang II in the stimulation of vasopressin re lease from rat hypothalamo-neurohypophysial explants [24], and has similar cardiovascular actions to Ang II when injected into the dorsal medulla of rats [25]. Evi dence for the neurosecretion of Ang II by the ME into portal blood includes immunocytochemical studies at both the light [26][27][28][29][30][31] and ultrastructural level [31 ] which show heavy staining of nerve terminals in the external lamina of the ME, in a manner similar to that for known adenohypophysial releasing factors [30]. At the ultrastructural level Ang II-immunopositive terminals are present in close proximity to the basement membrane surrounding the perivascular spaces of fenestrated blood vessels [31].…”

“…Evi dence for the neurosecretion of Ang II by the ME into portal blood includes immunocytochemical studies at both the light [26][27][28][29][30][31] and ultrastructural level [31 ] which show heavy staining of nerve terminals in the external lamina of the ME, in a manner similar to that for known adenohypophysial releasing factors [30]. At the ultrastructural level Ang II-immunopositive terminals are present in close proximity to the basement membrane surrounding the perivascular spaces of fenestrated blood vessels [31]. Ang II-immunoreactive fibers situated along the capillary loops of the external lamina of the ME show increased staining after adrenalectomy [30], consistent with a role for Ang II in pituitary release of ACTH.…”