114
Physiopathological Mechanisms of RH in Obesity/Metabolic
Syndrome
While studies report that 30–40% of RH are obese [ 196 – 198 ], the ESC Arterial
Hypertension Guidelines [ 199 ] suggest that weight loss leads to control of hyper-
tension with less medication [ 200 , 201 ]. Therefore, it is possible that obesity-
associated hypertension may fall out of criteria for true RH and become essential
hypertension, since it can be controlled with less than three drugs.
Moreover, the reversibility of RH through weight loss could signify that the
obesity- associated hypertension is transiently resistant and does not involve exactly
the same mechanisms as “true” RH. Hence, one can describe different entities which
only in specific contexts manifests a resistance (transient or sustained) to treatment.
A solid argument that supports this hypothesis is the lack of response to renal dener-
vation in obesity-associated RH [ 202 ].
However, weight loss reverses some of the physiopathological mechanisms,
decreasing sympathetic activation, plasma renin activity, and circulating leptin and
insulin levels, while determining an improvement in blood pressure and in vasodila-
tory effect of adiponectin and diminishing other risk factors for atherosclerosis
[ 203 ]. Nevertheless, recent research shows that blood pressure decrease reported in
weight loss studies may not be sustained, regardless of weight status, which raises
the need for long-term studies.
The phenotype of RH in obesity comprises insulin resistance and obesity/proin-
flammatory molecules, together with the correlation between demographics, life-
style, genetic factors, and environmental fetal programming [ 204 ]. Within this
framework, insulin resistance holds an important place due to its involvement in
activation of sympathoadrenal system, which, converging with increased glomeru-
lar filtration of glucose doubled by its reabsorption accompanied by sodium, leads
to hypervolemia and increased levels of sodium and calcium in vascular walls [ 205 ].
Thus, the spasm generated determines the increase of peripheral vascular tension,
while narrowing of the vessels due to insulin-stimulated fibroblast and vascular
smooth muscle cell proliferation leads to activation of RAAS and, finally, hyperten-
sion [ 206 ].
Another factor contributing to the pathogenesis of obesity-associated RH is rep-
resented by abnormal production of adipocytokines [ 207 ] such as leptin, resistin,
perivascular relaxation factors, and adiponectin triggered by excessive fat mass
[ 208 ], which results in imbalances in blood pressure control and, due to their func-
tions as inflammatory, immune, or hormonal signalers, has an impact on insulin
resistance and cardiovascular risk [ 209 ]. Moreover, they are correlated with hyper-
activity of sympathetic and RAAS and contribute to the target-organ damage associ-
ated with HT, being involved in the development of arterial stiffness [ 210 ]. Research
advances the hypothesis that adipokines are the missing link between insulin resis-
tance and obesity, as they are the pivotal element that links the external factors
involved in obesity pathogenesis with the molecular elements generating the cluster
A. Burlacu and A. Covic