The potential role of endothelin-l (ET-1) in essential hypertension in
humans is still subject to debate. We recently reported strong sodium
retention and renal vasoconstriction during pathophysiological increm
ents in plasma ET-1. Apart from this vasoconstrictor action, ET-1 also
has mitogenic properties that play a role in the pathophysiology of h
ypertension. On the other hand, some data refute an important role of
ET-1 in hypertension. We therefore investigated in nine subjects with
essential hypertension the constrictor actions of ET-1 by challenging
these subjects with a systemic infusion of ET-1 (0.5 ng/kg per minute
for 60 minutes, then 1.0 ng/kg per minute for 60 minutes, and finally
2.0 ng/kg per minute for 60 minutes). Furthermore, we studied whether
these effects of ET-1 could be modulated by oral use of the angiotensi
n-converting enzyme inhibitor enalapril (20 mg BID) or the calcium cha
nnel blocker nifedipine (60 mg OD). ET-1 infusion increased plasma ET-
1 levels from 2.5+/-0.4 to 11.6+/-1.0 pmol/L (P<.05). Blood pressure r
ose by approximately 10 mm Hg (P<.05). Cardiac index decreased by 21+/
-2%, whereas calculated systemic vascular resistance increased by 27+/
-6% (P<.05). Renal blood flow decreased from 1051+/-94 to 707+/-60 mL/
min at the end of the ET-1 infusion (P<.05), and calculated renal vasc
ular resistance increased from 118+/-19 to 189+/-19 mm Hg.min/L (P<.05
). Sodium excretion decreased from 227+/-39 to 111+/-15 mu mol/min (P<
.05). Both enalapril and nifedipine treatment prevented the systemic e
ffects of ET-1 infusion in these subjects. However, during enalapril t
reatment, despite renal predilatation, ET-1 reduced renal blood flow (
from 1119+/-132 to 701+/-75 mL/min, P<.05) and increased renal vascula
r resistance (from 111+/-16 to 187+/-28 mm Hg.min/L, P<.05) to the sam
e levels as during ET-1 infusion alone. Nifedipine pretreatment attenu
ated the ET-l-induced fall in renal blood flow (from 1088+/-93 to 907/-68 mL/min) and increase in renal vascular resistance (from 105+/-9 t
o 133+/-10 mm Hg.min/L). Although neither drug modulated the antinatri
uretic effect of ET-1, nifedipine increased basal sodium excretion (P<
.05), which compensated for the decrease during ET-1 infusion. In conc
lusion, essential hypertensive subjects are sensitive to the vasoconst
rictor effects of ET-1. Both enalapril and nifedipine can prevent the
systemic effects of ET-1, but nifedipine seems more effective in atten
uating the renal constrictor effects of ET-1.