Endothelin receptor antagonists (ETRA) are actively developed by the pharma
ceutical industry for several cardiovascular indications. In the context of
hypertension, preclinical studies are increasingly focused on prevention o
r regression of end-organ damage and drug combination than on control of ar
terial pressure in monotherapy, as most experimental models have already be
en studied. In general, the antihypertensive effect of ETRA is limited but
the overwhelming efficacy of this class of drugs to prevent several endorga
n damages warrants judicious combination. However, the few studies looking
at regression of hypertension-induced cardiovascular alterations proved les
s successful, suggesting that ETRA should be used early in the treatment of
hypertension to obtain full benefit. Judging from the progression of ongoi
ng trials and the development of new trials patients suffering from pulmona
ry hypertension and heart failure may be the first to benefit from this new
class of drugs. However, it is expected that once on the market, responsiv
e subsets of hypertensive patients will be identified and will benefit from
end-organ protection.