Cytochromes in hypertension
Cytochrome P450 (CYP) is a large family of oxidase enzymes known for their association with haem cofactors. Emerging evidence suggests that CYPs function as important regulators of cardiovascular and renal functions. In particular, CYP epoxygenases produce epoxyeicosatrienoic acids (EETs), which have vasodilatory and natriuretic properties and reduce blood pressure (BP) and hypertension. The main objective of the EU-funded RENAL FUNCTIONS/EETS (Role of epoxyeicosatrienoic acids in the regulation of blood pressure, renal hemodynamics and sodium excretion in renovascular model of hypertension) project was to define the role of EETs in BP regulation. For this purpose, scientists used the rat model of renovascular two kidney one clip (2K1C) hypertension and investigated the outcome of inhibiting epoxyde hydrolase (she), the enzyme that degrades EETs. Overall, hypertensive 2K1C rats expressed lower levels of EETs and administration of an she inhibitor enhanced the bioavailability of EETS and decreased BP. In addition, inhibition of she improved renal characteristics, including haemodynamics and function. Then, scientists utilised pressure myograph to determine changes in functional responsiveness to EETs. Interestingly, they observed that arteries from hypertensive rats exhibited decreased vascular dilation to EETs compared to arteries from animals with normal BP. These attenuated responses might further impair renal function in hypertension, underscoring the importance of EET signalling in addition to EET bioavailability. Findings of the RENAL FUNCTIONS/EETS project demonstrated the role of cytochrome P450 metabolites in the regulation of renal functions and BP. This knowledge advances our understanding of the multifactorial mechanisms that contribute to hypertension and has the potential to improve disease management.
Keywords
Cytochromes, hypertension, cytochrome P450, blood pressure, RENAL FUNCTIONS/EETS
