111cussed in section the section on Neurogenic Pathways, bone marrow is involved as
well in neuroinflammation, since it is the source for the proliferation of peripheral
inflammatory cells and their transport into the brain [ 30 ].
Therapeutic correlation Clinical trials have investigated the effects of antioxidants
in hypertensive patients, and although they have not proven to be an operational
treatment, current research advances the idea of targeting Noxs in an isoform-
specific manner in the attempt to balance the levels of oxidative stress.
The hypothesis of RH as autoimmune disease is completed by the involvement
of complement system and standard and high-sensitive C reactive protein [ 175 ],
their increased levels being reflected in the endothelial damage and arterial stiffness
[ 176 , 177 ]. Currently, the role of matrix metalloproteinases/tissue inhibitors of
metalloproteinases (MMPs/TIMPs) system in the pathogeny of hypertension is
being investigated, indicating a possible contribution to the determination of arterial
function [ 178 ].
Therapeutic correlation Aside from providing partial control of resistant hyperten-
sion, renal denervation brings supplementary evidence as to the sympathetic con-
trol of chronic vascular inflammation [ 179 , 180 ], since the procedure has beneficial
outcomes in the decrease of inflammation biomarkers and reduced T-cell activation
as well [ 181 ].
Genetic Perspectives on Resistant Hypertension
Each previous section on physiopathological mechanisms of RH (neural, RAAS, Na,
inflammation) includes gene involvement and influence on the various sites, such as
receptor, ligand, enzyme, or intracellular mechanism. Mutations in the gene that codes
the respective receptor/enzyme/ligand lead to dysregulation of the entire mechanisms
and, consequently, to an exaggerated pressor response or insufficient inhibition.
An excellent summarization of the research on gene variants involvement in RH
was recently published by El Rouby and Cooper-DeHoff [ 182 ].
We identified three main directions in the approach of RH gene framework:
- Understanding of the mechanisms behind the inadequate/exaggerated pressor
response - Understanding the reasons for the absence of response to usual antihypertensive
medication - Elaboration of new treatment approaches
Mainly, the pharmacogenomics of RH envisages the identification of genetic
markers for the prediction of the response to antihypertensive medication, therefore
optimizing the treatment scheme and possibly decreasing prevalence of RH [ 183 ].
Response or lack thereof to treatment is associated with several gene polymor-
phisms (e.g., ADRB1, CACNB2, NEDD4L) [ 184 ].
7 Pathophysiological Insights in Resistant Hypertension