Prolonged anti-hypertensive effects of oral sitaxsentan, a selective ET(A) endothelin receptor antagonist, in spontaneoulsy hypertensive hamsters.
BACKGROUND
The purpose of this study was to determine whether prolonged oral therapy with sitaxsentan, a potent selective ET(A) endothelin receptor antagonist, normalizes systolic blood pressure in spontaneously hypertensive hamsters, a new rodent model of high-renin genetic hypertension.


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).


CONCLUSIONS
Collectively, these proof-of-principle data indicate that prolonged oral sitaxsentan therapy normalizes systolic blood pressure in spontaneously hypertensive hamsters. We suggest that selective ET(A) endothelin receptor blockade could be beneficial in the treatment of essential hypertension associated with high renin plasma levels.
Rubinstein
Israel
I
Departments of Medicine and Biopharmaceutical Sciences, Colleges of Medicine and Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. IRubinst@uic.edu
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006224:Cricetinae; D065130:Endothelin A Receptor Antagonists; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D013876:Thiophenes / Q000494:pharmacology*
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D007555:Isoxazoles; D013876:Thiophenes; C106276:sitaxsentan