Enhanced expression of endothelin-1 gene may cause blood pressure-independent vascular hypertrophy.
Endothelin-1 (ET-1) has hypertrophic and mitogenic properties. Enhanced ET-1 gene expression in blood vessels of deoxycorticosterone acetate (DOCA)/salt hypertensive rats and DOCA/salt spontaneously hypertensive rats (SHRs) was previously demonstrated. In this study, the effect on ET-1 gene expression in blood vessels and on vascular hypertrophy of the development of hypertension of DOCA/salt hypertensive rats, and that of salt and DOCA, were investigated in Sprague-Dawley rats and in SHRs. Increased abundance of ET-1 mRNA and a greater content of immunoreactive ET-1 were found with progression of hypertension in the aorta and the mesenteric arterial bed only in DOCA/salt hypertensive rats and in DOCA/salt SHRs. Vascular expression of ET-1 was not enhanced in DOCA- or salt-treated rats, even when blood pressure rose to a mean systolic pressure of 210 mm Hg. The media thickness and the media cross-sectional area of mesenteric resistance arteries of all groups of rats, including SHRs and Wistar-Kyoto (WKY) rats, exhibited a close correlation with systolic blood pressure. In DOCA/salt hypertensive rats after 5 weeks and in DOCA/salt SHRs in which significant over-expression of ET-1 was present in blood vessels, vascular morphometric parameters were excessive for the level of systolic blood pressure. In DOCA/salt hypertensive rats and DOCA/salt SHRs treated with the combined ETA/ETB endothelin receptor antagonist bosentan, vascular morphometry correlated more closely with blood pressure, even though the blood pressure was only slightly lower than that of untreated rats. Lumen diameter correlated with blood pressure in all groups, including those overexpressing ET-1. These data support the hypothesis that ET-1 gene overexpression in blood vessels may accentuate vascular hypertrophy, but not remodeling, in DOCA/salt hypertensive rats and DOCA/salt SHRs in excess of that caused by blood pressure elevation per se.
Schiffrin
E L
EL
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Larivière
R
R
Li
J S
JS
Sventek
P
P
Touyz
R M
RM
D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000473:pathology*; D003900:Desoxycorticosterone; D016232:Endothelins / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D006973:Hypertension / Q000473:pathology; D006984:Hypertrophy; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D003900:Desoxycorticosterone