Hypertension promotes atherosclerosis and is a major source of morbidity and mortality. We show that mice lacking T and B cells (RAG-1-/- mice) have blunted hypertension and do not develop abnormalities of vascular function during angiotensin II infusion or desoxycorticosterone acetate (DOCA)-salt. Adoptive transfer of T, but not B, cells restored these abnormalities. Angiotensin II is known to stimulate reactive oxygen species production via the nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase in several cells, including some immune cells. Accordingly, adoptive transfer of T cells lacking the angiotensin type I receptor or a functional NADPH oxidase resulted in blunted angiotensin II-dependent hypertension and decreased aortic superoxide production. Angiotensin II increased T cell markers of activation and tissue homing in wild-type, but not NADPH oxidase-deficient, mice. Angiotensin II markedly increased T cells in the perivascular adipose tissue (periadventitial fat) and, to a lesser extent the adventitia. These cells expressed high levels of CC chemokine receptor 5 and were commonly double negative (CD3+CD4-CD8-). This infiltration was associated with an increase in intercellular adhesion molecule-1 and RANTES in the aorta. Hypertension also increased T lymphocyte production of tumor necrosis factor (TNF) alpha, and treatment with the TNFalpha antagonist etanercept prevented the hypertension and increase in vascular superoxide caused by angiotensin II. These studies identify a previously undefined role for T cells in the genesis of hypertension and support a role of inflammation in the basis of this prevalent disease. T cells might represent a novel therapeutic target for the treatment of high blood pressure.

/pdf/role-of-the-t-cell-in-the-genesis-of-angiotensin-ii-induced-53ojd8d3ig.pdf

Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction

Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses?

Fitzsimons, J. T. Angiotensin, Thirst, and Sodium Appetite. Physiol. Rev. 78: 583–686, 1998. — Angiotensin (ANG) II is a powerful and phylogenetically widespread stimulus to thirst and sodium appet...

Angiotensin, Thirst, and Sodium Appetite

In this review, the emerging functional roles of the brain angiotensin system have been considered. The major effects of Ang II can be classified into three groups, which imply three possible functions: The first, and largest, group is actions associated with the regulation of body fluid volume in response to hypovolemia. These include thirst, blood pressure increase, vasopressin release, sodium appetite and excretion, and ACTH and aldosterone release. This function alone has important implications for the control of blood pressure and the disease of hypertension. Another possible function is a role for angiotensin in the activity of gonadotropic hormone releasing hormones and pituitary hormones during the reproductive cycle and pregnancy. A third group of functions is the synaptic, neurotransmitter interactions of Ang II with catecholamines, serotonin, prostaglandins, and other peptides, not all of which could be reviewed here due to space limitations. This interaction is significant for all functions mentioned and leads to alterations in motivation (thirst, pain), memory (and possibly learning), and motor control. The amount of data available, however, is so limited that to claim angiotensin plays any major role in the latter functions would be premature. Throughout this review, we compared the central and peripheral effects of Ang II. We suggest that normally, a blood-CVO barrier prevents diffusion of peripheral Ang II to brain receptors inside the BBB. Because of this mechanism, the responses to the two routes of administration are distinctly different. When systemic peptide levels are low, Ang II activates only receptors in the CVOs; however, when these levels are high, the peptide diffuses to receptors that are normally activated only by brain Ang II.

Functions of Angiotensin in the Central Nervous System

Systemic osmoregulation is a vital process whereby changes in plasma osmolality, detected by osmoreceptors, modulate ingestive behaviour, sympathetic outflow and renal function to stabilize the tonicity and volume of the extracellular fluid. Furthermore, changes in the central processing of osmosensory signals are likely to affect the hydro-mineral balance and other related aspects of homeostasis, including thermoregulation and cardiovascular balance. Surprisingly little is known about how the brain orchestrates these responses. Here, recent advances in our understanding of the molecular, cellular and network mechanisms that mediate the central control of osmotic homeostasis in mammals are reviewed.

http://www.med.uottawa.ca/courses/nsc5104/assets/documents/dr_renaud2009/nrn2400.pdf

Central mechanisms of osmosensation and systemic osmoregulation.

Regional study of cerebral ventricle sensitive sites to angiotensin II

Lesions of the subfornical organ (SFO) severely attenuated drinking induced by injections of angiotensin II into the lateral ventricles, but a few days (4 to 14) later a recovery of the drinking response is observed. A possible explanation for this is that other dipsogenic sites are involved which are beyond the interventricular foramen and that SFO lesions produce an obstruction by edema or debris at the foramen which blocks access of cerebrospinal fluid-borne angiotensin to those sites. This hypothesis is supported by tracer studies and by direct injection into the third ventricle of SFO-lesioned animals. Other studies reported implicate the anteroventral third ventricle as a likely site for angiotensin receptors.

https://science.sciencemag.org/content/sci/190/4209/72.full.pdf

Ventricular obstruction: effect on drinking induced by intracranial injection of angiotensin.

Antidiuretic hormone release and the pressor response to central angiotensin II and cholinergic stimulation

Attenuated pressor responses to intracranially injected stimuli and altered antidiuretic activity following preoptic-hypothalamic periventricular ablation.

W.E. Hoffman

Papers

Regional study of cerebral ventricle sensitive sites to angiotensin II

Ventricular obstruction: effect on drinking induced by intracranial injection of angiotensin.

Antidiuretic hormone release and the pressor response to central angiotensin II and cholinergic stimulation

Attenuated pressor responses to intracranially injected stimuli and altered antidiuretic activity following preoptic-hypothalamic periventricular ablation.

The role of catecholamines in central antidiuretic and pressor mechanisms