Abstract P232: Endothelin B Receptor Modulation Of Diurnal Blood Pressure Amplitude During High Salt Diet

High salt diet can alter baroreflex sensitivity. We have previously shown that rats deficient in endothelin B receptors (ET B -R) demonstrate an exaggerated diurnal blood pressure amplitude similar to that seen in rats with sinoaortic denervation fed a high salt diet. However, it remains unclear if ET B -R influence on baroreflex function is due to sensory or efferent mechanisms of autonomic blood pressure control. We employed selective ET B -R antagonism using A192621 in ET B -R deficient rats (ET B -def) that only express functional ET B -R on efferent nerves and transgenic controls (TG) to isolate the role of efferent vs sensory pathways. Rats with telemetry were fed a normal salt diet (0.49% NaCl) during baseline and osmotic minipump infusion of 10 mg/kg/day A192621 or vehicle. After one week of infusion, animals were fed a high salt (4.0% NaCl) diet. Selective ET B -R blockade increased 24 hr MAP in TG animals during normal salt diet (+16.4 ± 1.0 mmHg from baseline; n = 10; p < 0.001) but had no effect on ET B -def (-1.2 ± 1.8 mmHg; n = 7; p > 0.99 ). A192621 treated TG rats did not exhibit a further increase in pressure following high salt diet (+5.5 ± 1.3 mmHg; n = 6; p = 0.25), but both vehicle and A192621 treated ET B -def rats displayed a salt-sensitive increase in MAP (+15.9 ± 4.2 and +14.4 ± 4.5 mmHg; n = 3 and 4; p = 0.003 and 0.001, respectively). A192621 treatment had no significant effect on MAP amplitude (light-dark difference) in any group during normal salt diet. However, during high salt, A192621 treated TG animals had an increase in MAP amplitude (+9.7 ± 0.7 mmHg; n = 6; p = 0.002), and vehicle had no effect (+0.8 ± 0.8 mmHg; n = 5; p = 0.97). Both A192621 and vehicle treated ET B -def rats had a similar increase in amplitude following high salt diet (+9.3 ± 0.6 and +8.6 ± 1.4; n = 4 and 3; p = 0.001 and 0.018, respectively). In summary, antagonism of ET B -R increased MAP only in TG rats but did not have an effect on diurnal amplitude during normal salt in any group. Antagonism of ET B -R during high salt diet caused TG rats to exhibit a similarly high diurnal amplitude as ET B -def rats. These data suggest that blocking ET B -R on baroreflex sensory pathways are the mitigating cause for increased diurnal blood pressure rhythms during high salt diet.