Background: The Renin Angiotensin System (RAS) is pharmacologically targeted to reduce
blood pressure, and patient compliance to oral medications is a clinical issue. The mechanisms
of action of angiotensin receptor blockers (ARBs) in reducing blood pressure are not well understood
and are purported to be via a reduction of angiotensin II signaling.
Objective: We aimed to develop a transdermal delivery method for ARBs (losartan potassium and
valsartan) and to determine if ARBs reveal a vasodilatory effect of the novel RAS peptide,
alamandine. In addition, we determined the anti-hypertensive effects of the transdermal delivery
Methods: In vitro and in vivo experiments were performed to develop an appropriate therapeutic system,
promising an alternative and more effective therapy in the treatment of hypertension. A variety
of penetration enhancers were selected such as isopropyl myristate, propylene glycol, transcutol and
dimenthyl sulfoxide to obtain a constant release of drugs through human skin. Small resistance vessels
(kidney interlobar arteries) were mounted in organ baths and incubated with an ARB. Vasodilatory
curves to alamandine were constructed.
Results: The in vivo studies demonstrate that systemic absorption of valsartan and losartan potassium
using the appropriate formulations provide a steady state release and anti-hypertensive effect even after
24 hours of transdermal administration. No apparent skin irritations (erythema, edema) were observed
with the tested formulations. We also show that blocking the AT1 receptor of rabbit interlobar
arteries in vitro reveals a vasodilatory effect of alamandine.
Conclusion: This study reveals the potential mechanism of AT1 receptor blockade via alamandine,
and is an important contribution in developing a favorable, convenient and painless antihypertensive
therapy of prolonged duration through transdermal delivery of AT1 blockers.