Carbon monoxide and hypertension

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The enzymatic action of haeme oxygenase yields carbon monoxide, biliverdin and iron. Carbon monoxide is implicated in many physiological processes, including the regulation of vascular tissue contractility and apoptosis. By stimulating the soluble guanylyl cyclase (sGC)/cGMP pathway and activating K+ channels in vascular smooth muscle cells (SMCs), carbon monoxide relaxes vascular tissues under physiological conditions. Altered metabolism and functions of carbon monoxide have been linked to the pathogenesis and maintenance of hypertension. The expression and activity of haeme oxygenase-1, sGC and cGMP in vascular SMCs are associated with different stages of development of hypertension in spontaneously hypertensive rats (SHRs). The importance of altered haeme oxygenase-2 expression in vascular tissues in hypertension remains unclear. Increased vascular contractility, unbalanced cellular apoptosis and proliferation in the vascular wall, increased oxidative stress, and the altered interaction of carbon monoxide and nitric oxide are among the consequences of haeme oxygenase/carbon monoxide system dysfunction in hypertension. Acute application of pharmacological inducers to upregulate the expression of haeme oxygenase-1 or the use of gene delivery method to overexpress haeme oxygenase-1 decreases blood pressure in young SHRs and other animal models of hypertension. These blood pressure-decreasing effects are annulled by metalloporphyrins. In adult SHRs, the haeme oxygenase/carbon monoxide system appears to be normalized as a compensatory reaction. To date, acute manipulation of the expression of haeme oxygenase-1 has not been successful in decreasing blood pressure in adult SHRs. In conclusion, abnormality of the haeme oxygenase/carbon monoxide system has a critical role in the pathogenesis of hypertension, and novel therapeutic approaches should be pursued to achieve selective improvement in the function of this system in hypertension.

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