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.