Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension
Status:
Unknown status
Trial end date:
2009-03-01
Target enrollment:
Participant gender:
Summary
BACKGROUND The effects of ACE-inhibitors on fibrinolysis are well documented. Experimental
and clinical studies have shown that ACE inhibitors induce a reduction in plasma PAI-1 levels
in many cardiovascular diseases, like hypertension, coronary heart disease, and heart
failure. Their effects on t-PA are more controversial, due to the fact that t-PA exists in
several forms, including free and bound to PAI-1. Indeed an increase in t-PA activity has
been observed in humans and it seems related to bradykinin increase which is known to
stimulate endothelial t-PA synthesis. These favourable effects on fibrinolysis could be
related not only to the Angiotensin II reduction and the bradykinin increase but also to the
improvement in insulin sensitivity, as insulin has been suggested as one of the main
regulators of fibrinolytic activity.
To date conflicting results have been reported about the effects of ARBs on fibrinolysis.
Some studies have reported small improvements, others no significant effect. These
conflicting results may be due to possible methodological bias but a possible
pathophysiological explanation might be that receptor subtypes other than AT1 mediate the
effect of Angiotensin-II on endothelial PAI-1 expression, i.e. the AT4 receptors, and during
AT1 receptor blockade there is an important increase not only of Angiotensin-II, but also of
all its catabolites including Angiotensin IV. The dissimilar effects on of ACE Is and ARBs
may also depend on their different action on the RAS and their different effect on insulin
sensitivity: ACE-Is improve insulin sensitivity, while the majority of ARBs have been
reported to have a neutral effect. Moreover, unlike ACE-Is, ARBs do not affect the metabolism
of bradykinin, which is known to stimulate t-PA synthesis and release.
AIM OF THE STUDY The aim of this study is to verify the effect of imidapril compared to
candesartan on insulin sensitivity, evaluated through the euglycemic hyperinsulinemic clamp,
and on fibrinolysis, evaluated through the plasma PAI-1 and t-PA activity, in mild to
moderate hypertensive patients.