Renal Effects of Endothelin-1 in Essential Hypertension

To the Editor: In their recent article, Dr Kaasjager and colleagues1 reported important data on the renal hemodynamic effects of endothelin-1 (ET-1) in 9 subjects with essential hypertension. They showed that ET-1 elicits a potent vasoconstrictor effect, which was found to be prominent in the renal vascular bed. The authors also showed that treatment with both the angiotensin-converting enzyme inhibitor enalapril and the dihydropyridine calcium channel blocker nifedipine could prevent the effects of ET-1 on systemic blood pressure, although only nifedipine seems to be effective in attenuating the renal constrictor effects of ET-1. Of interest, the authors measured the ET-1–induced changes of plasma renin activity (PRA) and plasma aldosterone levels but failed to detect any significant effect and thereby excluded that these hormones might account for their renal hemodynamic findings. In fact, contrary to what Kaasjager et al state, ET-1 infusion did induce a consistent 10% increase of plasma aldosterone both when administered alone (in the Control Study) and during enalapril or nifedipine treatment. This increase was seen even though the peptide was infused for only 180 minutes and at a dosage that produced a peak plasma concentration of immunoreactive ET-1 (11.6±1.0 pmol/L) which was subthreshold, ie, lower than the 30 to 300 pmol/L needed to elicit a vasoconstrictor response in various smooth muscle preparations in vitro.2 Because ET-1 was shown to enhance aldosterone secretion in different species, including humans, by acting on specific …