The role of angiotensin (1-7) in the regulation of renal function in rat models of hypertension

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Barry, Elaine Fiana
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University College Cork
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In the Spontaneously Hypertensive Rat (SHR), where, endogenous renal angiotensin II levels, angiotensin (1-7) levels, and mas receptor expression were similar to normotensive controls, intrarenal angiotensin (1-7) infusion caused a diuresis/natriuresis, the magnitude of which was similar between normotensive and SHR groups. A higher AT1 receptor expression in the SHR renal cortex appeared not to impact the excretory responses to intrarenal angiotensin (1-7) infusion. The diuretic/natriuretic response to exogenous angiotensin (1-7) was enhanced in the clipped kidney of the 2 kidney 1 clip (2K1C) models of hypertension, where angiotensin II levels were increased and AT1 receptor expression were reduced, with no major changes in angiotensin (1-7) concentration or mas receptor expression. The intrarenal angiotensin (1-7) infusion in the non-clipped kidney 2K1C group, where the endogenous cortical angiotensin (1-7) levels and AT1 receptor expression were increased, without changes to renal angiotensin II or mas receptor expression, elicited an anti-diuresis/anti-natriuresis. A similar excretory response to exogenous angiotensin (1-7) was elicited in the Deoxycorticosterone acetate - salt model of hypertension, where the angiotensin (1-7) levels and AT1 expression were increased and the angiotensin II levels and mas expression were decreased. Together, these studies demonstrated that the intrarenal infusion of exogenous angiotensin (1-7) could elicit altered acute renal excretory responses under various hypertensive conditions. The magnitude and directionality of the excretory response appeared to be dependent on the balance of activity levels between local endogenous angiotensin II/AT1 receptor axis and angiotensin (1-7)/mas receptor axis. The data generated support the hypothesis that there is a relationship between these two arms of the renin angiotensin system and that angiotensin (1-7) may have a counter-regulatory action on angiotensin II signalling. There is also evidence that under certain circumstances angiotensin (1-7) could exacerbate the actions of angiotensin II and may do so by binding at the AT1 receptor.
Angiotensin (1-7) , Hypertension , Hypertensive models , Renal , Renin angiotensin system
Barry, E. F. 2017. The role of angiotensin (1-7) in the regulation of renal function in rat models of hypertension. PhD Thesis, University College Cork.