HO-1 overexpression fails to attenuate hypertension when the NOS system is not fully operative

Abstract

Heme oxygenase (HO) is an enzyme that is involved in numerous secondary actions. One of its products, carbon monoxide (CO), seems to have an important but unclear role in blood pressure regulation. CO exhibits a vasodilatory action through the activation of soluble guanylyl cyclase and the subsequent production of cGMP.<br />The aim of the present study was to determine whether pathological and pharmacological HO-1 overexpression has any regulatory role on blood pressure in a renovascular model of hypertension. We examined the effect of zinc protoporyphyrin IX (ZnPP-IX) administration, an inhibitor of HO activity, on the mean arterial pressure (MAP) and heart rate (HR) in sham and aortic-coarcted rats and its interaction between the NOS pathway. The inhibition of HO increased MAP in normotensive rats with and without hemin pre-treatment but not in hypertensive rats. Pre-administration of L-NAME blocked the pressor response to ZnPP-IX, suggesting a key role of NOS in the cardiovascular action of HO inhibition. In the same way, aortic-coarcted rats, an experimental model of hypertension with impaired function and low expression of eNOS, did not show any cardiovascular response to inhibition or induction of HO. This finding suggests that eNOS is necessary for modulating the CO response in the hypertensive group. In conclusion, the present study suggests that HO regulates blood pressure through CO only when the NOS pathway is fully operative. In addition, chronic HO induction fails to attenuate the hypertensive stage induced by coarctation as a consequence of NOS pathway impairment.