Endothelin-1 gene expression in blood vessels and kidney of spontaneously hypertensive rats (SHR), L-NAME-treated SHR, and renovascular hypertensive rats.
Spontaneously hypertensive rats (SHR), renovascular hypertensive rats [two-kidney one clip Goldblatt (2-K 1C) and 1-K 1C], and SHR treated with the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), do not respond to endothelin (ET) receptor antagonists with a decrease in blood pressure. However, treatment with ET receptor antagonists has shown some beneficial renal and coronary effects in SHR. In this study we examined tissues from SHR, L-NAME-treated SHR, 2-K 1C, and 1-K 1C, using in situ hybridization with a specific rat preproET-1 cRNA probe to evaluate preproET-1 mRNA abundance in blood vessels, heart, and kidneys. Grain density was similar in SHR and Wistar-Kyoto (WKY) rats in all tissues examined. L-NAME-treated SHR showed increased grain density vs. SHR in endothelium of aorta and of small coronary arteries and in kidney glomeruli, but not in renal or mesenteric arteries. 2-K 1C presented increased grain density in coronary arteries and in glomeruli of the unclipped but not the clipped kidney vs. glomeruli of control rats. 1-K 1C rats exhibited increases in preproET-1 mRNA relative to unilaterally nephrectomized control rats in endothelium of aorta and in mesenteric and coronary arteries, but not in renal arteries or glomeruli. None of the hypertensive models studied showed detectable evidence of myocardial overexpression of preproET-1 mRNA. Therefore, tissue-specific enhancement of ET-1 expression may underlie ET-dependent functional alterations and may explain the beneficial effects of ET receptor antagonists in the coronary circulation or in the kidney in some hypertensive models, but not in SHR.
Deng
L Y
LY
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Schiffrin
E L
EL
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D006978:Hypertension, Renovascular / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D011498:Protein Precursors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester