115of conditions associated with obesity such as metabolic syndrome, inflammatory
and/or autoimmune diseases, and rheumatic diseases [ 211 , 212 ].
Adiponectin, either systemically derived or from perivascular fat, promotes
endothelial-dependent vasodilation [ 213 ]. These effects are diminished with obesity
in which low levels of plasmatic adiponectin generate higher NO inactivation and
decreased NO production [ 214 ].
Therapeutic correlation An optimized treatment for RH associated with obesity
will have to take into account the design of strategies for the regulation of adipokine
synthesis and release.
On the other hand, studies report the interaction between adipokines and the
immune system, since decreased leptin levels reduce T-cell responses [ 215 ], while
several inflammatory conditions have been associated with modified adipokine lev-
els. Additionally, interleukin-6 and TNF-α secreted by adipocytes trigger the induc-
tion of CRP production and lead to installation of inflammatory state [ 216 ]. High
levels of adipose stem cell proliferation, resulting in increased synthesis of inflam-
matory cytokines, have been correlated with impaired blood pressure control in
obese subjects [ 213 ]. However, the mechanisms by which adipokines intervene in
the etiopathogenic process of hypertension have not been completely elucidated
[ 217 ].
The central control mechanism of hypertension is also impaired by obesity, as
experimental studies report that the sympathoinhibitory reflexes such as the barore-
flex arc and the reflex induced by the gastrointestinal hormone cholecystokinin are
significantly diminished by abnormal weight, resulting from aberrant central signal-
ing triggering decreased responses of rostroventrolateral medulla neurons [ 218 ].
Finally, experimental studies reported that the insulin receptor substrate 2 (IRS2)
intervenes in the effect elicited by the action of insulin on proximal tubule transport,
through the insulin/PI3-K pathway, with specific regulatory mechanisms [ 219 ]. It is
therefore possible that preserved stimulation of this mechanism could modulate the
etiopathogenic process of obesity-associated hypertension.
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7 Pathophysiological Insights in Resistant Hypertension