Endothelin-1 in angiotensin II-dependent hypertension Answer to the Letter to the Editor

Abstract

We are delighted that our paper [1] succeeded in generating interest and discussion. Gardiner and Bennett raised an important issue concerning the potential role of endothelin-1 (ET-1) in the high blood pressure (BP) of transgenic TGR(mREN-2)27 rats [2], a monogenic renin-dependent model of severe hypertension. As far as we can understand, they found a slow-onset hypotensive effect during an acute 8 hr infusion of a mixed ETA/ETB receptor antagonist (SB 209670) in male heterozygous TGR(mREN-2)27 rats, where they recorded invasively intra-arterial blood pressure [3]. This hypotensive effect was surpassed by that induced by losartan. Interestingly, a synergistic hypotensive effect of the two drugs was also noticed. Based on this evidence Gardiner and Bennett would seem to caution on our statement that ET-1 does not play a major role in this form of hypertension. In a previous study in female heterozygous TGR(mREN-2)27 rats we had also found that the BP in vivo and the aortic contractile responses in vitro followed parallel changes with ageing. We therefore suggested that ET-1 could play a role in this model of hypertension [4]. However, chronic studies with ET antagonists in younger rats have given opposite results. In 25 day-old male heterozygous HanRen2/Edin-rats, derived from crossing homozygous TGR(mREN-2)27 with …