Aging Impairs Renal Autoregulation in Mice

Abstract

Impaired renal autoregulation permits more transmission of disturbance in systemic blood pressure, which initiates barotrauma in intrarenal microvasculatures such as glomerular and tubulointerstitial capillaries, contributing to the development of kidney damage and deterioration in renal function, especially under the conditions with high blood pressure. Although it has been postulated that autoregulatory efficiency is attenuated in the aging kidney, direct evidence remains lacking. In the present study, we measured the autoregulation of renal blood flow (RBF), myogenic response of afferent arteriole (Af-Art), tubuloglomerular feedback (TGF) in vivo with micropuncture, as well as TGF in vitro in isolated perfused juxtaglomerular apparatus (JGA) in young and aged C57BL/6 mice. We found that RBF was not significantly changed in response to a defined elevation of renal arterial pressure in young mice, but significantly increased in aged mice. Additionally, myogenic response of Af-Art measured by microperfusion with a stepwise increase in perfusion pressure was significantly blunted in the aging kidney, which is associated with the attenuation of intraluminal pressure-induced intracellular calcium increases, as well as the reduced expression of integrin α5 in Af-Art. Moreover, both TGF in vivo and in vitro were nearly inactive in the aging kidney, which is associated with the significantly reduced expression of adenosine A1 receptor (A1AR) and suppressed vasoconstrictor response to adenosine in Af-Art. In conclusion, this study demonstrates that aging impairs renal autoregulation with blunted myogenic response and inhibited TGF response. The underlying mechanisms involve the downregulations of integrin α5 and A1AR in the Af-Art.