163There are many different mechanisms by which vascular dysfunction contributes
to the vicious circles discussed here, the ones involving the multiple relations
between CKD, resistant hypertension, and autonomic dysfunction. In this highly
complex context, it is known that deficit of nitric oxide (NO) and baroreflex dys-
function associate with various cardiovascular conditions. There is this interesting
example of most recent finding with possible wide impact: sinocarotid baroreceptor
artificial stimulation in rabbits enhanced the vasodilation induced by the NO donor
sodium nitroprusside [ 73 ]. On the other side, one should keep in mind that auto-
nomic dysfunction, as in sympathetic overactivation, could actually favor arterial
dysfunction, as it has been shown that arterial baroreflex dysfunction promotes the
development of atherosclerosis in rats and owing to inflammatory mechanisms [ 74 ].
Many studies, both in experimental models and in human subjects, have described
the relation between hypertension and arterial stiffness, but connection to the arte-
rial baroreflex has been more thoroughly addressed only recently, when it was
shown, for example, that arterial stiffness, not strictly related to endothelial dys-
function, contributes to abnormal baroreflex in patients with hypertension [ 75 ].
Within this line of evidence it had been already suggested that reduced baroreflex
sensitivity may be relevant for the pathophysiology of hemodialysis patients with
vascular calcification [ 76 ], while one of our recent studies shows as well that vol-
ume overload in hemodialysis patients contributes to increased arterial stiffness but
without affecting endothelium-independent or endothelium-dependent arterial reac-
tivity [ 77 ].
We believe that, especially regarding such intricate mechanisms, careful results
interpretation in the current knowledge context is crucial, as in the case of this study
suggesting that “primary hypertension can be attributed to a mechanogenic etiology
without challenging current conceptions of renal and sympathetic nervous system
function” [ 78 ]. Refined multiparameter analysis indicates that estimation of barore-
flex sensitivity using the causal method is the best marker for autonomic nervous
system function [ 79 ].
Very fine control of intrarenal pressures and blood flow rate is ensured under
normal conditions, while in CKD such regulatory mechanisms are progressively
affected. So, there is a related substantial interest in the general features and mecha-
nisms for vascular smooth muscle contractile activity and for the ways this is influ-
enced by neural and humoral factors. But, aspects particular to the afferent and
efferent arterioles are at least as important, if not even more, as suggested by an
example of recent progress in understanding such differences based on the func-
tional implications of certain subtypes of voltage-dependent calcium channels [ 80 ].
Peritoneal dialysis is useful in CKD, but it leads to a further increase of arterial
stiffness together with a further decrease of baroreflex sensitivity [ 81 ]. Along with
the various intended beneficial effects on renal and cardiovascular function, renal
transplantation seems able to also normalize baroreflex sensitivity, and this occurs
together with a decrease in the stiffness of central arteries [ 82 ]. Last but not least,
spontaneous baroreflex indices correlate to local carotid mechanical properties, an
aspect that should be considered when discussing baroreflex function in both patho-
logical and normal conditions [ 83 ].
10 Secondary Causes: Work-Up and Its Specificities in CKD: Influence of Autonomic...