DEOXYCORTICOSTERONE ACETATE PLUS SALT INDUCES OVEREXPRESSION OF VASCULAR ENDOTHELIN-1 AND SEVERE VASCULAR HYPERTROPHY IN SPONTANEOUSLY HYPERTENSIVE RATS

Endothelin-1 gene expression is enhanced in the aorta and mesenteric a rteries, and possibly other vessels, of deoxycorticosterone acetate (D OCA)-salt hypertensive rats. In contrast, endothelin-1 gene expression is normal or reduced in spontaneously hypertensive rats (SHR). Severe vascular hypertrophy is present in DOCA-salt hypertensive rats but no t in SHR. In this study we investigated whether treatment of SHR with DOCA and salt would result in enhanced endothelin-1 expression and at the same time in severe vascular hypertrophy. Increased abundance of e ndothelin-1 mRNA was found in the aorta and the mesenteric arterial be d of SHR treated simultaneously with DOCA and salt but not when rats w ere treated with either separately. The wet weight of the aorta and of the mesenteric arterial bed, media thickness, media cross-sectional a rea, and media-to-lumen ratio of mesenteric small arteries of DOCA-sal t-treated SHR were exaggerated beyond what could be explained by the e levation of blood pressure, relative to SHR treated with salt or with DOCA, which did not overexpress vascular endothelin-1. In conclusion, SHR may exhibit enhanced expression of the endothelin-1 gene in blood vessels when treated with DOCA and salt, and associated with this ther e is severe vascular hypertrophy. These data support the hypothesis of a role of endothelin-1 in vascular hypertrophy.