engleski

EVALUATION OF VASCULAR RESPONSES TO ANGIOTENSIN II AND ANGIOTENSIN-(1-7) AFTER HYPERBARIC OXYGENATION AND THE ROLE OF EPOXYEICOSATRIENOIC ACIDS

Objective To investigate whether hyperbaric oxygenation (HBO) modulates vascular reactivity to angiotensin II (ANG II) and angiotensin-(1- 7) (ANG-(1-7)) in healthy and diabetic rats and to assess the role of epoxyeicosatrienoic acids (EETs) and CYP enzymes in the modulation of vascular reactivity by HBO. Design and Methods Isolated aortic ring preparations were used to test vascular reactivity (functional studies) to ANG II and ANG-(1-7) in healthy and diabetic rats (treated with an intermittent HBO protocol compared to nontreated), and a selective inhibitor of EETs synthesis (MS-PPOH) was used to assess the functional role of EETs. In vivo studies of HBO effects on arterial blood pressure were conducted, as well as molecular studies of the effects of HBO on oxidative stress indicators, serum concentration of ANG- (1-7), mRNA expression (qPCR) and protein expression (Western blot) of CYP enzymes in healthy and diabetic rats. Results HBO did not significantly change aortic reactivity to ANG II in healthy and diabetic rats. Vascular responses to the combination of ANG II + ANG- (1-7) were lower compared to ANG II contractions in healthy HBO rats, whereas such a difference was not present in untreated rats. HBO significantly increased aortic responses to ANG-(1-7) alone in healthy and diabetic animals. MS-PPOH reversed all effects of HBO on facilitation of vascular responses to ANG-(1- 7). There were no significant changes in arterial pressure, oxidative stress and serum ANG-(1-7) levels. HBO significantly increased mRNA expression of CY4A1 in healthy and CYP2J3 in diabetic rats, while CYP2C11 protein expression was significantly increased by HBO in diabetic rats. Conclusion HBO facilitates responses to ANG-(1- 7), while EETs seem to play an important role in the mechanism of this modulation. HBO increases the expression of specific CYP isoforms. The changes in vascular reactivity were not a consequence of changes in arterial pressure, oxidative stress or ANG-(1- 7) blood levels.

angiotensin II; angiotensin-(1-7); hyperbaric oxygenation; epoxyeicosatrienoic acids

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