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Articles in PresS, published online ahead of print June 6, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00522.2001
Submitted on August 29, 2001
Accepted on May 31, 2002
-Hydroxylase Activity
1 Department of Biopharmaceutical Sciences, University of California San Francisco, San Francisco, CA, USA
2 Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA
3 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: deanna{at}itsa.ucsf.edu.
The cytochrome P450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor which is implicated in the regulation of blood pressure. The identification of selective inhibitors of renal 20-HETE formation for use in vivo would facilitate studies to determine the systemic effects of this eicosanoid. We characterized the acetylenic fatty acid sodium 10-undecynyl sulfate (10-SUYS) as a potent and selective mechanism-based inhibitor of renal 20-HETE formation. A single dose of 10-SUYS caused an acute reduction in mean arterial blood pressure in 8 wk old spontaneously hypertensive rats. The decrease in mean arterial pressure was maximal 6 hr after 10-SUYS treatment (17.9 ± 3.2 mm Hg; p<0.05) and blood pressure returned to baseline levels within 24 hr after treatment. Treatment with 10-SUYS was associated with a decrease in urinary 20-HETE formation in vivo and attenuation of the vasoconstrictor response of renal interlobar arteries to angiotensin II in vitro. These results provide further evidence that 20-HETE plays an important role in the regulation of blood pressure in the spontaneously hypertensive rat.
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