Rapid Communication Effect of a Nonselective Endothelin Antagonist on Vascular Remodeling in Deoxycorticosterone Acetate-Salt Hypertensive Rats Evidence for a Role of Endothelin in Vascular Hypertrophy
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چکیده
We have previously shewn that the endothelin content in arteries of deoxycorticosterone acetate (DOCA)salt hypertensive rats is increased. We designed this study to examine, using the new orally active nonselective endothelin receptor antagonist bosentan, whether this increase in vascular endothelin may contribute to elevated blood pressure and vascular hypertrophy in DOCA-salt hypertensive rats. Rats received bosentan (100 mg/kg body wt per day) for 3 weeks mixed with their food. Systolic blood pressure of DOCA-salt hypertensive rats rose to 197±5 mm Hg, and that of bosentantreated DOCA-salt hypertensive rats was 177±4 mm Hg (P<.01). Mesenteric resistance arteries were studied on a wire myograph. The media width, ratio of media width to lumen diameter, and cross-sectional area of the media of resistance arteries of bosentan-treated DOCA-salt hypertensive rats Endothelins comprise a family of potent vasoconstrictor peptides' endowed, as other similar peptides, with mitogenic properties. The role of endothelins in hypertension is unclear. Endothelin-1 (ET-1) is one of the best-studied and possibly one of the more important members of this family of peptides in peripheral tissues. Several studies have demonstrated that the circulating concentrations of ET-1 exhibit little or no increase in most models of hypertension in animals or in human essential hypertension." It has also been shown that the effects of ET-1 on blood vessels in experimental models of hypertension and in essential hypertensive humans are either normal or blunted. Thus, it has been difficult to postulate a role of ET-1 in hypertension. We have recently demonstrated that in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat the content of immunoreactive ET-1 is increased in aorta and mesenteric arteries despite normal circulating levels. Thus, endothelin secretion may occur abluminally, and exaggerated vascular production may not result in elevated plasma levels. Histochemical staining for endothelin was enhanced in endotheReceived March 10, 1994; accepted in revised form May 16, 1994. From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal (Canada). Reprint requests to Ernesto L. Schiffrin, MD, PhD, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, Quebec, Canada H2W 1R7. © 1994 American Heart Association, Inc. were significantly smaller than those of untreated DOCA-salt hypertensive rats. The lumen diameter and cross-sectional area of the media of vessels of bosentan-treated rats were not different from those of uninephrectomized control rats. Vasoconstrictor responses, which were altered in DOCA-salt hypertensive rats, approached control in the bosentan-treated rats. We conclude that these results with a nonselective endothelin receptor antagonist may suggest a role for endothelin in the elevation of blood pressure and vascular hypertrophy and remodeling in DOCA-salt hypertensive rats. (Hypertension. 1994^4:183-188.)
منابع مشابه
Exaggerated vascular and renal pathology in endothelin-B receptor-deficient rats with deoxycorticosterone acetate-salt hypertension.
BACKGROUND Endothelin (ET)-1 plays an important role in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt-induced hypertension. We evaluated the pathological role of ET(B) receptors in DOCA-salt-induced hypertension, cardiovascular hypertrophy, and renal damage by using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the ET(B) receptor gene. METHODS AND...
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