Hypertension is a complex interplay of interrelated etiologies, and the leading risk factor for many cardiovascular morbidity
and mortality worldwide. Cardinal pathophysiological features of hypertension include enhanced vascular inflammation, vascular remodeling,
vascular contractility and increased oxidative stress. In response to oxidative, inflammatory or other noxious stimuli, many
physiological pathways like the heme oxygenase (HO) system are activated in an attempt to counteract tissue insults. However, the
pathophysiological activation of the HO system only results to a transient increase of HO activity that fall below the necessary threshold
capable of activating the downstream signaling components of the HO system like the soluble guanylyl cyclase (sGC)/cyclic guanosine
monophosphate (cGMP) secondary messenger system. Therefore, a more robust potentiation of the HO system by pharmacological
agents such as hemin, heme-arginate, cobalt protoporphyrin or through retroviral HO-1 gene delivery would be needed to surmount the
threshold for cytoprotection. The HO system modulates cellular homeostasis. Importantly, the HO system plays a vital role in a wide
spectrum of physiologic including the regulation of blood vessel tone. Alterations in the activity and expression of HO has been correlated
to pathophysiology of hypertension and related complications such as hypertrophy, myocardial infarction and heart failure. Moreover,
the cytoprotection exerted by HO is attributable to its catabolic products namely, carbon monoxide, bilirubin/biliverdin, and ferritin
that are known to modulate immune, inflammatory and oxidative insults.
The growing incidence of hypertension and associated cardiometabolic complications has prompted the need for the exploration of
alternative therapeutic strategies like substances capable of potentiating the HO system. This review briefly, highlights the functional significance
of the HO system and its downstream signaling molecules including bilirubin/biliverdin, carbon monoxide and ferritin as potential
therapeutic modalities for the management of hypertension and its related co-morbid conditions.
Keywords: Hemeoxygenase, Adiponectin, Oxidative stress, Inflammation, Carbon Monoxide, Bilirubin, Biliverdin, Ferritin, Angiotensin-
Induced Hypertension, Renovascular Hypertension, Pulmonary Hypertension, Diabetic Spontaneously Hypertension, Portal Hypertension,
Fructose-Induced Hypertension, Salt-Induced Hypertension, Essential Hypertension.
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