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(Hypertension. 1997;30:15-21.)
© 1997 American Heart Association, Inc.

Articles

Endothelin-1–Induced Vasopressor Responses in Essential Hypertension

Karin A. H. Kaasjager; Hein A. Koomans; ; Ton J. Rabelink

From the Department of Nephrology and Hypertension, University Hospital Utrecht (The Netherlands).

Correspondence to T.J. Rabelink MD, PhD, Department of Nephrology and Hypertension (F03.226), University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands.

Abstract The potential role of endothelin-1 (ET-1) in essential hypertension in humans is still subject to debate. We recently reported strong sodium retention and renal vasoconstriction during pathophysiological increments in plasma ET-1. Apart from this vasoconstrictor action, ET-1 also has mitogenic properties that play a role in the pathophysiology of hypertension. 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 angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel 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 rose 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 vascular resistance increased from 118±19 to 189±19 mm Hg·min/L (P<.05). Sodium excretion decreased from 227±39 to 111±15 µmol/min (P<.05). Both enalapril and nifedipine treatment prevented the systemic effects of ET-1 infusion in these subjects. However, during enalapril treatment, despite renal predilatation, ET-1 reduced renal blood flow (from 1119±132 to 701±75 mL/min, P<.05) and increased renal vascular resistance (from 111±16 to 187±28 mm Hg·min/L, P<.05) to the same levels as during ET-1 infusion alone. Nifedipine pretreatment attenuated the ET-1–induced fall in renal blood flow (from 1088±93 to 907±68 mL/min) and increase in renal vascular resistance (from 105±9 to 133±10 mm Hg·min/L). Although neither drug modulated the antinatriuretic effect of ET-1, nifedipine increased basal sodium excretion (P<.05), which compensated for the decrease during ET-1 infusion. In conclusion, essential hypertensive subjects are sensitive to the vasoconstrictor effects of ET-1. Both enalapril and nifedipine can prevent the systemic effects of ET-1, but nifedipine seems more effective in attenuating the renal constrictor effects of ET-1.

Key Words: endothelin • hypertension, essential • calcium channel blockers • angiotensin-converting enzyme inhibitors

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