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Prolonged Anti-Hypertensive Effects of Oral Sitaxsentan, a Selective ETA Endothelin Receptor Antagonist, in Spontaneoulsy Hypertensive Hamsters

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Abstract

Introduction

The purpose of this study was to determine whether prolonged oral therapy with sitaxsentan, a potent selective ETA endothelin receptor antagonist, normalizes systolic blood pressure in spontaneously hypertensive hamsters, a new rodent model of high-renin genetic hypertension.

Materials and Methods

Spontaneously hypertensive hamsters received either oral sitaxsentan (15 mg kg−1 day−1) dissolved in high purity water or saline for 7 weeks. Systolic blood pressure was monitored in lightly anesthetized animals using the leg-cuff method.

Results

We found that sitaxsentan elicited a significant decrease in systolic blood pressure in spontaneously hypertensive hamsters from 175 ± 6 mmHg at baseline to 109 ± 7 mmHg after 7 weeks (p < 0.05). Although treatment of spontaneously hypertensive hamsters with saline was also associated with a significant decrease in systolic blood pressure from baseline, the magnitude of response was significantly less than that observed with sitaxsentan (p < 0.05).

Discussion

Collectively, these proof-of-principle data indicate that prolonged oral sitaxsentan therapy normalizes systolic blood pressure in spontaneously hypertensive hamsters. We suggest that selective ETA endothelin receptor blockade could be beneficial in the treatment of essential hypertension associated with high renin plasma levels.

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Authors and Affiliations

  1. Departments of Medicine and Biopharmaceutical Sciences, Colleges of Medicine and Pharmacy, University of Illinois at Chicago, Chicago, IL, 60612, USA

    Israel Rubinstein

  2. Jesse Brown VA Medical Center, Chicago, IL, 60612, USA

    Israel Rubinstein

  3. Department of Medicine (M/C 719), University of Illinois at Chicago, 840 South Wood Street, Room 913-N, Chicago, IL, 60612-4325, USA

    Israel Rubinstein

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  1. Israel Rubinstein
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Correspondence to Israel Rubinstein.

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Rubinstein, I. Prolonged Anti-Hypertensive Effects of Oral Sitaxsentan, a Selective ETA Endothelin Receptor Antagonist, in Spontaneoulsy Hypertensive Hamsters. Cardiovasc Drugs Ther 20, 387–390 (2006). https://doi.org/10.1007/s10557-006-0293-1

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  • DOI: https://doi.org/10.1007/s10557-006-0293-1

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