Effect of chronic treatment of adult spontaneously hypertensive rats with an endothelin receptor antagonist.
We previously showed that endothelin-1 expression was increased in vascular endothelium of deoxycorticosterone acetate-salt hypertensive rats, whereas in spontaneously hypertensive rats (SHR) it is similar to or less than that in normotensive rats. Treatment with the combined endothelin type A/endothelin type B receptor antagonist bosentan moderately reduced blood pressure rise and nearly completely blunted the development of vascular hypertrophy, particularly in small arteries, in the deoxycorticosterone acetate-salt hypertensive model, suggesting a paracrine role for vascular endothelin-1 in the induction of blood vessel hypertrophy in some forms of experimental hypertension. In the present study we examined the effect of chronic oral treatment for 4 weeks of 12-week-old SHR and Wistar-Kyoto rats (WKY) with 100 mg/kg per day bosentan. Blood pressure rose to hypertensive levels similarly in bosentan-treated and untreated SHR; systolic pressure of WKY was also unaffected. The wet weights of the heart, of aortic segments, and of the mesenteric arterial bed were similar in treated and untreated SHR. When coronary, renal arcuate, mesenteric, and femoral small arteries were evaluated on a wire myograph, the media width and media-to-lumen ratio were greater and the lumen diameter was smaller in vessels from SHR relative to those from WKY, except in small arteries from the renal cortex, in which the lumen was not significantly different in both strains. The media cross-sectional area of small arteries fom the four vascular beds was similar in both strains. Identical morphometric parameters were found in the four vascular beds in bosentan-treated and untreated rats of eh strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
J S
JS
MRC Multidisciplinary Research Group on Hypertension, University of Montréal, Quebec, Canada.
Schiffrin
E L
EL
D000284:Administration, Oral; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D000077300:Bosentan; D006332:Cardiomegaly / Q000188:drug therapy; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013449:Sulfonamides / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000804:Angiotensin II; D000077300:Bosentan