Enhanced expression of the endothelin-1 gene in blood vessels of DOCA-salt hypertensive rats: correlation with vascular structure.
Endothelin (ET)-1 is a potent vasoconstrictor peptide which is also endowed with hypertrophic and mitogenic properties. Enhanced ET-1 gene expression in blood vessels of rats with hypertension induced by deoxycorticosterone acetate (DOCA)-salt has been previously demonstrated. The objective of this study was: (1) to investigate the individual effects of salt and DOCA, and of the development of hypertension in DOCA-salt-hypertensive rats, on ET-1 gene expression in blood vessels; and (2) to correlate the presence of enhanced ET expression and the severity of vascular hypertrophy. By providing salt and/or DOCA to rats which were or were not unilaterally nephrectomized, groups of rats with variable degrees of blood pressure elevation were generated. Increased abundance of ET-1 mRNA and a greater content of immunoreactive ET-1 were found with progression of hypertension in aorta and the mesenteric arterial bed only in unilaterally nephrectomized DOCA-salt-treated rats (DOCA-salt-hypertensive rats). Vascular expression of ET-1 was not enhanced in other DOCA-or salt-treated rats, even when blood pressure rose to a mean systolic pressure of 180 mm Hg. The wet weight of aorta and the mesenteric arterial bed, the media thickness, the media cross-sectional area, and the media-to-lumen ratio of mesenteric small arteries of all groups of rats exhibited a close correlation with systolic blood pressure. In DOCA-salt-hypertensive rats after 5 weeks, in which overexpression of ET-1 was maximal, the vascular morphometric parameters were excessive for the level of systolic blood pressure. However, in DOCA-salt-hypertensive rats treated with the combined ETA/ETBET receptor antagonist bosentan, vascular morphometry correlated closely with blood pressure, even though blood pressure was only slightly lower than than of untreated DOCA-salt-hypertensive rats. These data support the hypothesis that ET-1 gene overexpression in blood vessels may accentuate vascular hypertrophy in some forms of hypertension.
Schiffrin
E L
EL
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Canada.
Larivière
R
R
Li
J S
JS
Sventek
P
P
D000818:Animals; D001011:Aorta / Q000473:pathology; D001483:Base Sequence; D001794:Blood Pressure; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012965:Sodium Chloride
D019332:Endothelin-1; D015335:Molecular Probes; D012333:RNA, Messenger; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D012083:Renin