Aging impairs renal autoregulation
Authors: Wei Jin , Zhang Jie , Jiang Shan , Wang Lei , Liu Ruisheng 
Published: June 2021

Renal autoregulation maintains renal blood flow (RBF) and glomerular filtration rate constant over a wide range in systolic blood pressure. Renal autoregulation is primarily regulated by two mechanisms, which are myogenic and tubuloglomerular feedback (TGF) responses. Although evidence from experimental and clinical studies suggested that aging may impair vasoregulatory mechanisms, age‐related alterations in renal autoregulation remain elusive. In the present study, we hypothesized that aging impairs renal autoregulation by altering both myogenic response and TGF. To test our hypothesis, autoregulation of RBF, myogenic response in isolated afferent arteriole (Af‐Art) and TGF response in vivo were measured in young (3 months) and aged (24 months) C57BL/6 male mice.

Renal autoregulation was evaluated by changes in RBF while adjusting renal perfusion pressure (RPP) by aorta coarctation above renal arteries. In young mice, a decrease in RPP by 28.86±4.1 mmHg (from 87.31±2.7 to 58.45±3.4 mmHg) had no significant change in RBF. Whereas, in aged mice, a decrease in RPP by 26.76±3.2 mmHg (from 86.54±3.7 to 59.78±2.6 mmHg) reduced RBF by 33.8±5.6%.

Then we measured myogenic response in the isolated perfused Af‐Art. The Af‐Arts constricted by 24.7±4.1% in young mice, while it was only 11.9±3.2% in aged mice when the intraluminal pressure was increased from 60 to 140 mmHg. In addition, we measured changes in intracellular calcium concentration ([Ca2+]i) in smooth muscle cells (SMCs) in response to an increase in perfusion pressure with fura‐2 AM in the isolated perfused Af‐Art. Pressure induced [Ca2+]i increase in SMCs of Af‐Art was significantly lower in aged mice (11.4±3.6%) than in young mice (42.2±3.2%). To investigate the mechanism, we measured the mRNA expressions of ion channels and intracellular factors involved in the mechanotransduction of pressure in the Af‐Arts. Among the ion channels and intracellular factors, voltage‐gated L‐type Ca2+ channels (L‐VOCC) was the most downregulated gene with 89.73±5.52% reduction in the Af‐Arts in aged mice compared with young mice. Furthermore, inhibition of L‐VOCC by nifedipine eliminated the differences in myogenic response and pressure induced intracellular Ca2+ changes in Af‐Arts between young and aged mice.

Finally, TGF response in vivo, as indicated by the maximal change of stop flow pressure, was measured by micropuncture. TGF was 5.5±0.5 mmHg in young mice and significantly blunted to 0.9±0.7 mmHg in aged mice. To investigate the mechanism, we measured the mRNA expression of adenosine A1 receptor in Af‐Arts. The expression of A1 receptor was decreased by 82.26±15.35% in the Af‐Arts of aged mice compared with young mice. Furthermore, we measured a dose (10−10–10−7mol/l) response curve of adenosine in isolated perfused Af‐Arts. Adenosine induced a dose‐dependent constriction of Af‐Arts in young mice with a maximal constriction by 23.5±4.2% at 10−7 mol/l. Whereas, the adenosine‐induced vasoconstriction was abolished in aged mice.

In conclusion, autoregulation of RBF, myogenic response of the Af‐Art and TGF response in vivo were impaired in aged mice than young mice. The potential underlying mechanisms may be involved in reduced expression levels of L‐VOCC and adenosine A1 receptor in the Af‐Art. These changes may contribute to the glomerular injury, reduced renal functional reserve and the development of chronic kidney disease in aging.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.