Therapeutic potential of carbon monoxide in hypertension-induced vascular smooth muscle cell damage revisited: From physiology and pharmacology

As a chronic and progressive disorder, hypertension remains to be a serious public health problem around the world. Among the different types of hypertension, pulmonary arterial hypertension (PAH) is a devastating disease associated with pulmonary arteriole remodeling, right ventricular failure and death. The contemporary management of systemic hypertension and PAH has substantially grown since more therapeutic targets and/or agents have been developed. Evolving treatment strategies targeting the vascular remodeling lead to improving outcomes in patients with hypertension, nevertheless, significant advancement opportunities for developing better antihypertensive drugs remain. Carbon monoxide (CO), an active endogenous gasotransmitter along with hydrogen sulfide (HS) and nitric oxide (NO), is primarily generated by heme oxygenase (HO). Cumulative evidence suggests that CO is considered as an important signaling molecule under both physiological and pathological conditions. Studies have shown that CO confers a number of biological and pharmacological properties, especially its involvement in the pathological process and treatment of hypertension-related vascular remodeling. This review will critically outline the roles of CO in hypertension-associated vascular remodeling and discuss the underlying mechanisms for the protective effects of CO against hypertension and vascular remodeling. In addition, we will propose the challenges and perspectives of CO in hypertensive vascular remodeling. It is expected that a comprehensive understanding of CO in the vasculature might be essential to translate CO to be a novel pharmacological agent for hypertension-induced vascular remodeling.