Adrenergic dependence of the endothelin‐mediated pressor response in Dahl salt‐resistant and salt‐sensitive rats

We have previously shown that selective endothelin A (ET A ) receptor antagonism augments the stress‐mediated rises in arterial pressure and norepinephrine in Dahl salt‐resistant (DR), but not salt‐sensitive (DS) rats. Since these effects were absent during mixed ET A/B receptor blockade, we tested the hypothesis that there is greater adrenergic dependence of the ET B ‐mediated pressor response in DR vs. DS rats. Pressor responses to the selective ET B receptor agonist sarafotoxin (S6c) were examined in anesthetized male DR and DS rats during ganglion blockade. S6c produced comparable dose‐dependent increases in arterial pressure in both DR and DS rats. In DR rats, pretreatment with the selective α 1 adrenergic antagonist prazosin (PZ; 1 mg/kg) blunted the peak pressor response to 0.1 (17±2 vs. 24±2 mmHg, PZ vs. untreated, p<0.05) and 1 nmol/kg S6c (23±2 vs. 35±4 mmHg, PZ vs. untreated, p<0.01). Peak pressor response to 1 nmol/kg S6c was also lower in DS rats treated with PZ (20±4 vs. 47±12 mmHg, PZ vs. untreated, p<0.01). There was a greater reduction in the steady‐state response to 1 nmol/kg S6c in treated DS (‐3+4 vs. 35±16 mmHg, PZ vs. untreated) than in DR rats (14±2 vs. 24±6 mmHg, PZ vs. untreated). Together, these data suggest that the pressor response to ET B receptor activation is partially dependent on α 1 adrenergic stimulation; however, the adrenergic component is not enhanced in DR vs. DS rats.