Plasma aldosterone regulation in anephric man.

Renin-angiotensin system: biochemistry and mechanisms of action.

In recent years, the focus of interest on the role of the renin-angiotensin system (RAS) in the pathophysiology of hypertension and organ injury has changed to a major emphasis on the role of the local RAS in specific tissues. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by independent multiple mechanisms. Proximal tubular angiotensinogen, collecting duct renin, and tubular angiotensin II type 1 (AT1) receptors are positively augmented by intrarenal Ang II. In addition to the classic RAS pathways, prorenin receptors and chymase are also involved in local Ang II formation in the kidney. Moreover, circulating Ang II is actively internalized into proximal tubular cells by AT1 receptor-dependent mechanisms. Consequently, Ang II is compartmentalized in the renal interstitial fluid and the proximal tubular compartments with much higher concentrations than those existing in the circulation. Recent evidence has also revealed that inappropriate activation of the intrarenal RAS is an important contributor to the pathogenesis of hypertension and renal injury. Thus, it is necessary to understand the mechanisms responsible for independent regulation of the intrarenal RAS. In this review, we will briefly summarize our current understanding of independent regulation of the intrarenal RAS and discuss how inappropriate activation of this system contributes to the development and maintenance of hypertension and renal injury. We will also discuss the impact of antihypertensive agents in preventing the progressive increases in the intrarenal RAS during the development of hypertension and renal injury.

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

Circulation: Overall Regulation

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

Native Australian and introduced species of animals are adapted to severe sodium deficiency. Effects of such a deficiency are aggravated by pregnancy and lactation, and it has been shown that mechanisms controlling sodium homeostasis in wild rabbits are subject to profound stress.

Physiological, Morphological and Behavioural Adaptation to a Sodium Deficient Environment by Wild Native Australian and Introduced Species of Animals

SOME GENERAL CONSIDERATIONS Clinical There is evidence that increased secretion of aldosterone is a contributory cause of oedema occurring in kidney, liver and heart disease. The term ' contributory ' is used in the sense of implying that a number of factors act concurrently in the developed clinical state, and it would be unusual for oedema formation to be simply and commensurately attributable to any one of them alone. Thus administration to normal men of doses of aldosterone considerably larger than the inferred daily secretion in man with congestive cardiac failure did not produce oedema.1 Oedema is not a characteristic sign in the aldosterone secreting tumours which were first described by Conn.2, 3 Similarly with adrenalectomized dogs, Gross and Lichtlen' found that very large doses of aldosterone did not produce oedema. On the other hand, Davis, Pechet, Ball and Goodkinds found that aldosterone secretion was increased in dogs with experimental right heart lesions which caused congestive failure, and in dogs with thoracic inferior vena cava constriction producing ascites. If such dogs were adrenalectomized, administration of adequate electrolyte-active hormone was essential for oedema formation to occur.6 The developed clinical syndromes are similar to many other physiological responses and pathological states in so far as the ' cause ' is identifiable as the concurrent action of a number of factors which are severally necessary and jointly sufficient. In the particular instance of cardiac oedema, substantial studies have been made to evaluate other factors postulated in the ' forward ' and ' backward failure theories, and we do not propose to ente this discussion here. It is this multiplicity of concomitant and conse quent phenomena in clinical conditions whic Inakes elucidation so difficult. As an example w may consider the enormous excretion of aldo sterone by nephrotic patients. Using promising new modification of the original isoto dilution method7, 8 of estimating aldosteron secretion, Ulick, Laragh and Lieberman9 foun up to 6,600 T/day. The etiology of nephrosis i unknown and therefore the direct effect of th etiological conditions on the adrenal cannot b tested. It is possible that the nephrotic kidne produces a substance which activates the adren but this hypothesis cannot be tested until suc material is identifiable by assay. Through un known mechanisms the excess secretion mav resul from disturbance of electrolyte levels or dis tribution or from abnormal distribution of bod fluid. Abnormal metabolic degradation of aldo sterone by the liver or other tissues may cau excess secretion through some feed-back mecha nism to the adrenal. The elucidation of an clinical condition is impossible without under standing every phenomenon in the disea mechanism to the stage where each can b separately identified both qualitatively an quantitatively.

https://pmj.bmj.com/content/postgradmedj/36/412/76.full.pdf

The control of aldosterone secretion.

BLAIR-WEST, J. R., J. I? COGHLAN, D. A. DENTON, J. W. FUNDER, B. A. SCOGGINS, AND R. D. WRIGHT. Inhibition of renin secretion by systemic and intrarenal angiotensin infusion. Am. J. Physiol. 220(5): 1309-1315. 197 1 .-Conscious sheep were allowed to become sodium depleted by loss of parotid saliva for 24 or 48 hr. Angiotensin II was infused continuously intravenously at 10, 20, or 60 pg/hr or into the renal artery at 3 or 6 pg/hr during a 24-hr control period and throughout the period of sodium depletion. Intravenous infusion of angiotensin II prevented the usual increase of plasma renin concentration (PRC) during the first 24 hr of sodium loss and blunted the PRC response over the next 24 hr. When the infusion was stopped, PRC increased within 2 hr to high levels. Continuous intrarenal infusion of angiotensin II caused similar inhibition of PRC rise during 24 hr of sodium depletion without effect on systemic blood angiotensin II concentration, systemic blood pressure, plasma [K], or renal sodium excretion. It is concluded that the inhibition of renin release during sodium depletion was due to a direct intrarenal action of angiotensin II at physiological concentration in blood. Renin secretion may be regulated partly by a short-loop negative feedback mechanism.

R. D. Wright

Papers

Physiological, Morphological and Behavioural Adaptation to a Sodium Deficient Environment by Wild Native Australian and Introduced Species of Animals

The control of aldosterone secretion.

The control of aldosterone secretion.

Inhibition of renin secretion by systemic and intrarenal angiotensin infusion

Osmoregulatory thirst in sheep is disrupted by ablation of the anterior wall of the optic recess.