New Cardiovascular and Pulmonary Therapeutic Strategies Based on the Angiotensin-Converting Enzyme 2/Angiotensin-(1–7)/Mas Receptor Axis

Ferreira, Anderson J.; Murça, Tatiane M.; Fraga-Silva, Rodrigo A.; Castro, Carlos Henrique; Raizada, Mohan K.; Santos, Robson A. S.

Recently, a formulation based on the Ang-(1-7) included into hydroxypropyl β-cyclodextrin [HPβCD/Ang-(1-7)] was developed by Lula and colleagues [133] . Cyclodextrins are pharmaceutical tools used for design and evaluation of drug formulations, and they enhance the drug stability and absorption across biological barriers and offer gastric protection [134] . The amphiphilic character of cyclodextrins allows the possibility of formation of supramolecular inclusion complexes stabilized by noncovalent interactions with a variety of guest molecules [133, 134] . In this regard, the formulation HPβCD/Ang-(1-7) allowed the oral administration of Ang-(1-7). Pharmacokinetic and functional studies showed that oral HPβCD/Ang-(1-7) administration significantly increases plasma Ang-(1-7) levels and promotes an antithrombotic effect that was blunted in Mas deficient mice [135] . Marques and colleagues [136] have found that chronic oral administration of HPβCD/Ang-(1-7) significantly attenuates the heart function impairment and cardiac remodeling induced by isoproterenol treatment and myocardial infarction in rats [136] .