VASCULAR AND CARDIAC OVEREXPRESSION OF ENDOTHELIN-1 GENE IN ONE-KIDNEY, ONE-CLIP GOLDBLATT HYPERTENSIVE RATS BUT ONLY IN THE LATE-PHASE OF 2-KIDNEY ONE-CLIP GOLDBLATT HYPERTENSION

Objective To investigate a model of experimental hypertension that exh ibits severe hypertrophy of small blood vessels but in which deoxycort icosterone acetate (DOCA) and salt are absent: the one-kidney, one cli p model of Goldblatt renovascular hypertension, which is non-renin-dep endent, and compare it with the renin-dependent two-kidney, one clip G oldblatt 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 nephre ctomized rats, the aorta and mesenteric arteries exhibited a significa nt increase in the intensity of the 2.3 kb band corresponding to hybri dization with endothelin-1 messenger RNA (mRNA) in comparison with res ults obtained in control unilaterally nephrectomized rats, No increase was noted in the blood vessels of the two-kidney, one clip hypertensi ve rat at 2 or 4 weeks, but significant increases were found at 8 week s in aorta, but not in mesenteric arteries, Cardiac abundance of endot helin-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 (a t 8 weeks) in hue-kidney, one clip hypertensive rats. Conclusion Becau se one-kidney, one clip hypertensive rats presented severe vascular hy pertrophy whereas two-kidney, one clip hypertensive rats only did so i n the late phase of hypertension, these results lend further support t o there being a relationship between vascular hypertrophy and endothel in-1 vascular overexpression in experimental models of hypertension. T hey also demonstrate that enhancement of the expression of endothelin- 1 gene in blood vessels and in the heart of hypertensive rats may occu r in the absence of exposure to DOCA and salt, and that endothelin-1 g ene overexpression in experimental hypertension occurs early in non-re nin-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-con tracted two-kidney, one clip hypertensive rat.