Impaired myogenic responses of the Af‐Art contributes to chronic kidney disease in Milan Normotensive rats

Abstract

We have recently reported that the development of glomerular injury, proteinuria and chronic kidney disease (CKD) in Dahl Salt Sensitive and Fawn Hooded Hypertensive rats are associated with an impaired myogenic response of the afferent arteriole (Af-Art) and autoregulation of renal blood flow (RBF), whereas the myogenic response is enhanced in Spontaneously Hypertensive rats that are resistant to the development of renal disease. Milan normotensive rats (MNS) are more susceptible to development of CKD than the Milan Hypertensive rat (MHS) even though blood pressure is much lower. This study compared the myogenic response in the Af-Art and autoregulation of RBF in 6-9 week old MNS and MHS rats. Autoregulation of RBF was measured following an increase in renal perfusion pressure (RPP) from 100 to 140 mmHg. The diameter of Af-Art of MNS rats increased from 14.0 ± 0.5 to 14.1 ± 0.6 µm (n=6, p>0.05) in response to an increase in perfusion pressure from 60 to 120 mmHg. In contrast, the diameter of the Af-Art decreased significantly from 14.0 ± 0.8 to 11.7 ± 1.1 µm (n=6, p<0.05) in MHS rats. In vivo, MNS rats exhibited poor autoregulation of RBF, it increased by 27% when RPP was increased from 100 to 140 mmHg. In contrast, MHS rats exhibited nearly perfect autoregulation and RBF was not significantly altered. Glomerular capillary pressure estimated from measurement of proximal tubular stop flow pressure increased by 10 mmHg in MNS following the elevation in RPP, but not in MHS rats. These data indicate that impaired myogenic response of the Af-Art contributes to the progression of proteinuria and renal injury in MNS rats. This studies were supported by NIH Grants HL36279 and DK104184-01.