Endothelin-B (ET_B) receptors and blood pressure in experimental hypertension in rats

Endothelin-B receptors (ET_BR), located mainly on endothelial cells, produce vasodilator effects by releasing either nitric oxide (NO) and/or prostacyclin (PGI₂). Several reports have suggested impaired endothelial NO production in Dahl salt-sensitive (DS) rats. This impaired NO production complicates the understanding of the ET_BR response in this salt-sensitive model. The aim of the study reported here was to determine the physiological role of the ET_BR and the main pathway through which the receptors exhibit their effects in salt-sensitive hypertension, using DS rats. Hypertension was induced in the rats over a 4-week period by giving a 2% NaCl solution. The animals were divided into three groups. BQ-788 (a selective ET_BR antagonist) was given to the first group, to determine whether ET_BR played a role in blood pressure (BP) of hypertensive rats. L-NAME (NO synthase inhibitor) was given to the second group to determine the effects of NO on the BP of hypertensive rats. The third group received L-NAME + BQ-788, to determine the specific role of NO response to ET_BR activation. These drugs were administered intravenously and aortic BP recorded before and after the intervention. Administration of BQ-788 to rats pre-treated with L-NAME (group 3) showed a significant increase in all BP parameters measured. Similar diastolic BP results in the L-NAME and L-NAME + BQ-788 groups were observed. Since administration of the ET_BR antagonist in the rats pre-treated with L-NAME did not produce an intensified response compared to L-NAME alone, our results suggested that NO is probably the dominant factor in the ET_BR response in this salt-sensitive hypertension model.