Renin Angiotensin blockers and cardiac protection. From basis to clinical trials

Am J Hypertens. 2021 Jul 15:hpab108. doi: 10.1093/ajh/hpab108. Online ahead of print.ABSTRACTDespite a similar beneficial effect on blood-pressure lowering observed with ACEIs and ARBs, several clinical trials and meta-analyses have reported higher cardiovascular mortality and lower protection against myocardial infarction with ARBs when compared to ACEIs. The European guidelines for the management of coronary syndromes and European guidelines on diabetes recommend using ARBs in patients who are intolerant to ACEIs. We reviewed the main pharmacological differences between ACEIs and ARBs which could provide insights into the differences in the cardiac protection offered by these two drug classes. The effect of ACEIs on the tissue and plasma levels of bradykinin and on nitric oxide production and bioavailability is specific to the mechanism of action of ACEIs; it could account for the different effects of ACEIs and ARBs on endothelial function, atherogenesis and fibrinolysis. Moreover, chronic blockade of AT1 receptors by ARBs induces a significant and permanent increase in plasma angiotensin II and an over-stimulation of its still available receptors. In animal models, AT4 receptors have vasoconstrictive, proliferative and inflammatory effects. Moreover, in models with kidney damage, atherosclerosis, and/or senescence, activation of AT2 receptors could have deleterious fibrotic, vasoconstrictive and hypertrophic effects. seems prudent and reasonable to reserve the use of ARBs ...
Source: American Journal of Hypertension - Category: Cardiology Authors: Source Type: research