Role of endothelin in the development of dahl hypertension

Michael S. Goligorsky, Kazumoto Iijima, Maureen Morgan, Masashi Yanagisawa, Tomoh Masaki, Lang Lin, Alberto Nasjletti, Frederick Kaskel, Marshall Frazer, Kamal F. Badr

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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+]iresponse 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 prepro-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.

Original languageEnglish (US)
Pages (from-to)S484-S491
JournalJournal of Cardiovascular Pharmacology
Volume17
StatePublished - Jan 1 1991
Externally publishedYes

Keywords

  • Anthroylouabain
  • Fura-2
  • Immunoreactive endothelin
  • Mesangial cells
  • Ouabain
  • SBFI
  • Smooth muscle

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Goligorsky, M. S., Iijima, K., Morgan, M., Yanagisawa, M., Masaki, T., Lin, L., Nasjletti, A., Kaskel, F., Frazer, M., & Badr, K. F. (1991). Role of endothelin in the development of dahl hypertension. Journal of Cardiovascular Pharmacology, 17, S484-S491.