michigan hypertension core curriculum - State of Michigan

In the setting of chronic hypertension, the afferent arteriole anatomically remodels and
becomes functionally incapable of maximally dilating (figure 4). This causes the lower end of the
normal sigmoidal relationship between MAP and intraglomerular pressure to move to a higher
level of BP. In contradistinction to the effect of chronic hypertension on the cerebral blood flow
autoregulatory curve, as kidney function deteriorates and nephron number drops, the upper limit of
autoregulation moves to a lower BP level resulting in intraglomerular pressure (and GFR) varying
in a more direct relationship with systemic arterial pressure. In other words, the relationship
between glomerular pressure and GFR becomes more linear.
32 Hypertension Core Curriculum
Figure 4
As nephron number falls, the demands on the remaining glomeruli increase to make up for the lost
glomeruli. GFR is maintained, at the expense of high intraglomerular pressure, as a consequence
of local activation of the RAS system that causes Ang II-mediated efferent arteriolar constriction;
at the afferent arteriole, vasodilatory prostaglandins and nitric oxide mediate vasodilatation.
These changes in afferent and efferent arteriolar tone, in aggregate, lead to intraglomerular
capillary hypertension. There is also increased glomerular endothelial permeability resulting in
excess filtration of plasma proteins in direct relation to the increased glomerular pressure that
is, in turn, elevated because of transmission of systemic arterial pressure into a dilated afferent
arteriole. A final common pathway leading to further nephron destruction is glomerusclerosis and
tubulointerstitial fibrosis.
To understand the above pathophysiology is to also understand how to protect the
kidney from further loss of functioning mass. Attainment of low levels of BP as well as lowering
intraglomerular pressure with drugs such as angiotensin converting enzyme (ACE) inhibitors and/
or angiotensin receptor blockers (ARB’s) are proven ways to protect kidney function (figure 5).