Vascular and cardiac overexpression of endothelin-1 gene in one-kidney, one clip Goldblatt hypertensive rats but only in the late phase of two-kidney one clip Goldblatt hypertension.
OBJECTIVE
To investigate a model of experimental hypertension that exhibits severe hypertrophy of small blood vessels but in which deoxycorticosterone acetate (DOCA) and salt are absent: the one-kidney, one clip model of Goldblatt renovascular hypertension, which is non-renin-dependent, and compare it with the renin-dependent two-kidney, one clip Goldblatt hypertensive rat, in which additionally vascular hypertrophy is less severe.


METHODS
Endothelin-1 gene expression in blood vessels and in the heart was examined by Northern blot analysis.


RESULTS
After 2 or 4 weeks of application of the silver clip to unilaterally nephrectomized rats, the aorta and mesenteric arteries exhibited a significant increase in the intensity of the 2.3 kb band corresponding to hybridization with endothelin-1 messenger RNA (mRNA) in comparison with results obtained in control unilaterally nephrectomized rats. No increase was noted in the blood vessels of the two-kidney, one clip hypertensive rat at 2 or 4 weeks, but significant increases were found at 8 weeks in aorta, but not in mesenteric arteries. Cardiac abundance of endothelin-1 mRNA was also increased in ventricles and in the left atria of one-kidney, one clip hypertensive rats, but only in the late phase (at 8 weeks) in two-kidney, one clip hypertensive rats.


CONCLUSIONS
Because one-kidney, one clip hypertensive rats presented severe vascular hypertrophy whereas two-kidney, one clip hypertensive rats only did so in the late phase of hypertension, these results lend further support to there being a relationship between vascular hypertrophy and endothelin-1 vascular overexpression in experimental models of hypertension. They also demonstrate that enhancement of the expression of endothelin-1 gene in blood vessels and in the heart of hypertensive rats may occur in the absence of exposure to DOCA and salt, and that endothelin-1 gene overexpression in experimental hypertension occurs early in non-renin-dependent, volume-expanded models such as the one-kidney, one clip or the DOCA-salt hypertensive rat, but only in the progressively non-renin-dependent late phase of the initially renin-dependent volume-contracted two-kidney, one clip hypertensive rat.
Sventek
P
P
Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.
Turgeon
A
A
García
R
R
Schiffrin
E L
EL
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006978:Hypertension, Renovascular / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism* / Q000503:physiopathology; D008638:Mesenteric Arteries / Q000378:metabolism; D008955:Models, Cardiovascular; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012720:Severity of Illness Index; D013997:Time Factors
D019332:Endothelin-1; D012333:RNA, Messenger; D012083:Renin