Superoxide-dependent hypertension in male and female endothelin B receptor-deficient rats

Evidence for endothelin (ET) involvement in the control of fluid volume balance and arterial pressure has been derived in part from the observations that rats lacking the ET_B receptor develop hypertension when placed on a high-salt (HS) diet. The present study was designed to determine the effect of superoxide on salt-induced hypertension in male and female ET _B-deficient (sl/ sl) and wild-type control (wt) rats. After 14 days on a HS (8% NaCl) diet, female sl/sl rats had significantly elevated arterial pressure (183 ± 2 mm Hg, tail cuff) compared with female wt rats (134 ± 2 mm Hg). The response to a HS diet was lower in male sl/sl rats (166 ± 6 mm Hg) yet was significantly greater than that in male wt controls (135 ± 3 mm Hg). Separate groups of male and female sl/sl and wt rats were given tempol (1 mM in drinking water) during HS treatment. Arterial pressures were 149 ± 5 mm Hg in male and 143 ± 3 mm Hg in female sl/sl rats treated with tempol, values that were similar to those of controls on a normal salt diet. After 14 days, however, male and female sl/ sl rats recovered from the blood pressure-lowering effects of tempol. On Day 15, arterial pressures in female sl/sl rats on a HS diet were 160 ± 6 mm Hg and 177 ± 6 mm Hg in tempol-treated and untreated groups, respectively. In male sl/sl rats, arterial pressures were 155 ± 3 mm Hg and 165 ± 5 mm Hg in tempol-treated and untreated groups, respectively. On Day 15, no differences among groups with or without tempol were observed in plasma thiobarbituric acid-reactive substance (TBARS) concentrations or in urinary excretion of TBARS. Plasma ET-1 concentrations were significantly higher in female vs. male sl/sl rats. These results indicate that the early stages of salt-dependent hypertension produced by ET_B receptor deficiency are dependent on superoxide and that the elevated pressure in the female rats may be due to elevated circulating levels of ET-1.