PHYSIOLOGICAL ACTIONS OF THE RENIN-ANGIOTENSIN SYSTEM

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The purpose of this project is to study physiological and pathological aspects of the renin-angiotensin system, emphasising its role in circulatory homeostasis and development. During the past year studies have focused on a) the role of type-1 angiotensin II (Ang II) receptors located in parvicellular corticotropin-releasing hormone CRH and CRH/VP cells in the hypothalamic paraventricular nucleus (PVN), and b) the consequenses of chronic stress on the peripheral renin-Ang-aldosterone system. a) The regulation of Ang II receptors in the PVN by glucocorticoids and the role of Ang II regulating the responsiveness of the HPA axis during stress was studied by correlating Ang II receptor expression in the PVN with changes in activity of the HPA axis. Various stress paradigms increased Ang II receptor expression in the parvicellular subdivision of the PVN in similar fashion irrespective of their effect on the activity of the HPA axis. Ang II receptor expresion in parvicellular cells was reduced by adrenalectomy and increased by glucocorticoid administration. The stimulatory effect of stress on Ang II receptor expression in the PVN was prevented by adrenalectomy, indicating that glucocorticoids are necessary for the effect of stress. These data support a role for Ang II in the central mechanisms of adaptation to stress, but indicate that Ang II does not play a role controlling the responsiveness of the HPA axis. b) Repeated physical-psychological stress reduced basal and stimulated aldosterone secretion in spite of elevated basal plasma renin activity. The increases in plasma renin activity were associated with increases in renin mRNA expression in the kidney due to repeated sympathetic stimulation. In vitro studies revealed that while the early aldosterone biosynthetic pathway is increased, Ang II receptor content, mRNA levels and activity of aldosterone synthetase are decreased in chronically stress rats. The data provides evidence for a role of chronic stress in the development of hyperreninemic hypoaldosteronism.