Angiotensin, Thirst, and Sodium Appetite

Abstract

Angiotensin (ANG) II is a powerful and phylogenetically widespread stimulus to thirst and sodium appetite. When it is injected directly into sensitive areas of the brain, it causes an immediate increase in water intake followed by a slower increase in NaCl intake. Drinking is vigorous, highly motivated, and rapidly completed. The amounts of water taken within 15 min or so of injection can exceed what the animal would spontaneously drink in the course of its normal activities over 24 h. The increase in NaCl intake is slower in onset, more persistent, and affected by experience. Increases in circulating ANG II have similar effects on drinking, although these may be partly obscured by accompanying rises in blood pressure. The circumventricular organs, median preoptic nucleus, and tissue surrounding the anteroventral third ventricle in the lamina terminalis (AV3V region) provide the neuroanatomic focus for thirst, sodium appetite, and cardiovascular control, making extensive connections with the hypothalamus, limbic system, and brain stem. The AV3V region is well provided with angiotensinergic nerve endings and angiotensin AT1 receptors, the receptor type responsible for acute responses to ANG II, and it responds vigorously to the dipsogenic action of ANG II. The nucleus tractus solitarius and other structures in the brain stem form part of a negative-feedback system for blood volume control, responding to baroreceptor and volume receptor information from the circulation and sending ascending noradrenergic and other projections to the AV3V region. The subfornical organ, organum vasculosum of the lamina terminalis and area postrema contain ANG II-sensitive receptors that allow circulating ANG II to interact with central nervous structures involved in hypovolemic thirst and sodium appetite and blood pressure control. Angiotensin peptides generated inside the blood-brain barrier may act as conventional neurotransmitters or, in view of the many instances of anatomic separation between sites of production and receptors, they may act as paracrine agents at a distance from their point of release. An attractive speculation is that some are responsible for long-term changes in neuronal organization, especially of sodium appetite. Anatomic mismatches between sites of production and receptors are less evident in limbic and brain stem structures responsible for body fluid homeostasis and blood pressure control. Limbic structures are rich in other neuroactive peptides, some of which have powerful effects on drinking, and they and many of the classical nonpeptide neurotransmitters may interact with ANG II to augment or inhibit drinking behavior. Because ANG II immunoreactivity and binding are so widely distributed in the central nervous system, brain ANG II is unlikely to have a role as circumscribed as that of circulating ANG II. Angiotensin peptides generated from brain precursors may also be involved in functions that have little immediate effect on body fluid homeostasis and blood pressure control, such as cell differentiation...

Distinct neural mechanisms for the control of thirst and salt appetite in the subfornical organ

“…dehydration, hypovolemia, or hyponatremia) (Fitzsimons, 1998). The SFO has been reported to sense circulating Ang II to elicit water-drinking and salt-intake behaviors (Simpson and Routtenberg, 1973).…”

“…Previous studies reported that some neurons in the sCVOs, where AT1a is abundantly expressed, are activated by systemic Na depletion (Fitzsimons, 1998) and that the neural activities in Na-depleted animals are supressed by intracerebroventricular injection of AT1a antagonists along with the reduction of salt-intake behaviors . In the sCVOs, there also exists neurons activated by water depletion (Fitzsimons, 1998), and electrolytic lesions of the sCVOs reduced dipsogenic effects of Ang II (Simpson and Routtenberg, 1975;Lind and Johnson, 1983). These results indicate that the sCVOs are involved in drinking behaviors.…”

“…Renin cleaves angiotensinogen and produces Ang I. Subsequently, Ang I is further cleaved to form Ang II by angiotensin converting enzyme (Fitzsimons, 1998). Two receptor subtypes for Ang II, subtype 1 (AT1) and subtype 2 (AT2), have been identified in mammals (Timmermans et al, 1992).…”

Genomic Expression Systems on Hierarchy and Network Leading to Hypertension: Long on History, Short on Facts.

“…It is well established that the injection of angiotensin II into the brain causes significant physiological responses, including increases in blood pressure, drinking behavior, and vasopressin release (45). In addition to the hepatic production of angiotensinogen, it is known to be expressed in astrocytes in the brain (46,47).…”

Résultats de l’étude ALLHAT : un traitement uniformisé de l’hypertension artérielle?

“…Il n'est pas du tout impossible que l'action bénéfique de différentes classes d'agents antihypertenseurs puisse être différente entre le jeune hypertendu et la personne âgée lorsque certains segments de l'arbre vasculaire ou lorsque certains organes cibles sont déjà touchés de façon irréversible, pas toujours apparente cliniquement. De nombreuses observations fondamentales et cliniques récentes (intelligence-based medicine) examinent les phénomènes précoces qui caractérisent la maladie hypertensive: la sensibilité au chlorure de sodium [6], la rigidité des gros troncs artériels [7], les anomalies de la perméabilité endothéliale [8], le remodelage précoce vasculaire [9] et extra-vasculaire de la matrice interstitielle [10]. Certaines classes d'antihypertenseurs, tels que les IEC [11], plus récem-ment les antagonistes des récepteurs de l'angiotensine [12], enfin même certains diurétiques [13] ont montré non seulement une action palliative mais encore une action préventive sur les manifestations précoces de la maladie hypertensive.…”