Role of endothelin in the development of Dahl hypertension.
To evaluate the possible role of endothelin in the development and/or maintenance of hypertension in Dahl rats, we examined the responsiveness of isolated vascular smooth muscle and glomerular mesangial cells, as well as deendothelialized vascular ring preparations to endothelin-1 (ET-1). Production of immunoreactive endothelin (ir-ET) was studied in freshly isolated glomeruli and renal medullary slices. Both glomerular mesangial cells and vascular smooth muscle cells obtained from prehypertensive Dahl-S rats exhibited an exaggerated [Ca2+]i response to ET-1, as compared with cells obtained from Dahl-R rats. This was paralleled by the enhanced isometric contraction of vascular rings obtained from prehypertensive Dahl-S rats. ir-ET production was doubled in response to 0.1 mM ouabain in tissue samples obtained from prehypertensive Dahl-S, but not Dahl-R rats. This effect was not observed in tissues obtained from animals fed a 4% NaCl diet (hypertensive). Immunocytochemistry of ET distribution in the outer medullary stripe showed approximately a 40% higher fluorescence intensity in sections obtained from Dahl-S rats fed 4% NaCl diet as compared with Dahl-R rats fed the same diet. Northern blot analysis of poly(A)+ RNA extracted from medullae of prehypertensive Dahl-S and -R rats using a full-length cDNA probe for rat ET-1 revealed a marginal induction of pre-pro-ET-1 message in Dahl-S samples after 30 and 60 min of incubation with 0.1 mM ouabain. In conclusion, increased responsiveness of target cells to ET-1 and inducibility of ir-ET production in prehypertensive Dahl-S rats are in favor of a possible role of this peptide in the pathogenesis of Dahl hypertension. We hypothesize that ouabain-like factor(s) may trigger production of ET, thus serving as a link between high-salt intake and the development of hypertension in Dahl-S rats.
Goligorsky
M S
MS
State University of New York, Stony Brook 11794-8152.
Iijima
K
K
Morgan
M
M
Yanagisawa
M
M
Masaki
T
T
Lin
L
L
Nasjletti
A
A
Kaskel
F
F
Frazer
M
M
Badr
K F
KF
D000818:Animals; D015152:Blotting, Northern; D016232:Endothelins / Q000502:physiology*; D016257:Fura-2; D005920:Glomerular Mesangium / Q000378:metabolism; D006973:Hypertension / Q000209:etiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D016232:Endothelins; D012965:Sodium Chloride; D016257:Fura-2