ETA receptor blockade attenuates hypertension and decreases reactive oxygen species in ETB receptor-deficient rats

Ahmed Abdelrazik Elmarakby, E. Dabbs Loomis, Jennifer S. Pollock, David M. Pollock

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

We hypothesize that endothelin-A receptor stimulation contributes to the elevated blood pressure and superoxide production in endothelin-B receptor-deficient rats on a high salt diet. Experiments were conducted on homozygous endothelin-B-deficient (sl/sl) and wild-type rats (wt) fed a high salt diet (8% NaCl) for 3 weeks. Separate groups were given normal drinking water or water containing the endothelin-A receptor antagonist, ABT-627 (5 mg/kg per day; n = 8-9 in all groups). On a normal salt diet, (sl/sl) rats had a significantly elevated systolic blood pressure compared with wt (138 ± 3 vs 117 ± 4 mmHg, respectively; P < 0.05). High salt diet caused a significant increase in systolic blood pressure in (sl/sl) rats compared with wt (158 ± 2 vs 138 ± 3 mmHg, respectively; P < 0.05). Endothelin-A receptor blockade decreased systolic blood pressure in (sl/sl) rats on high salt (125 ± 5 mmHg; P < 0.05 vs without antagonist) without affecting the systolic blood pressure in wt (119 ± 4 mmHg). Aortic superoxide production (lucigenin chemiluminescence) and plasma 8-isoprostane were elevated in sl/sl rats and were significantly reduced by endothelin-A receptor blockade in sl/sl, but not in wt rats. These findings suggest that endothelin-1, through the endothelin-A receptor, contributes to salt-induced hypertension and vascular superoxide production in endothelin-B-deficient rats.

Original languageEnglish (US)
JournalJournal of Cardiovascular Pharmacology
Volume44
Issue numberSUPPL. 1
DOIs
StatePublished - Nov 1 2004

Fingerprint

Reactive Oxygen Species
Hypertension
Blood Pressure
Endothelin A Receptors
Salts
Superoxides
Diet
8-epi-prostaglandin F2alpha
Endothelins
Endothelin B Receptors
Endothelin-1
Luminescence
Drinking Water
Blood Vessels
Water

Keywords

  • Blood pressure
  • ET-deficient rats
  • High salt
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

ETA receptor blockade attenuates hypertension and decreases reactive oxygen species in ETB receptor-deficient rats. / Elmarakby, Ahmed Abdelrazik; Loomis, E. Dabbs; Pollock, Jennifer S.; Pollock, David M.

In: Journal of Cardiovascular Pharmacology, Vol. 44, No. SUPPL. 1, 01.11.2004.

Research output: Contribution to journalArticle

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