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

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.

• Authors: Ahmed A Elmarakby, E Dabbs Loomis, Jennifer S Pollock, David M Pollock
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 44 Suppl 1 Pg. S7-10 (Nov 2004) ISSN: 1533-4023 [Electronic] United States
• PMID: 15838363 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Endothelin A Receptor Antagonists
• Endothelins
• Pyrrolidines
• Receptor, Endothelin A
• Receptor, Endothelin B
• Sodium Chloride, Dietary
• Superoxides
• 8-epi-prostaglandin F2alpha
• Dinoprost
• Atrasentan

Topics

• Animals
• Animals, Genetically Modified
• Antihypertensive Agents (pharmacology)
• Aorta (drug effects, metabolism, physiopathology)
• Atrasentan
• Blood Pressure (drug effects)
• Dinoprost (analogs & derivatives, blood)
• Disease Models, Animal
• Down-Regulation
• Endothelin A Receptor Antagonists
• Endothelins (blood, urine)
• Hypertension (chemically induced, drug therapy, metabolism, physiopathology)
• Male
• Pyrrolidines (pharmacology)
• Rats
• Receptor, Endothelin A (metabolism)
• Receptor, Endothelin B (deficiency, genetics, metabolism)
• Sodium Chloride, Dietary
• Superoxides (metabolism)
• Time Factors