Abstract P107: Role for Endothelin B Receptors in the Maintenance of Heart Rate Baroreflex Function

Abstract

Rats lacking functional endothelin B (ET B ) receptors are hypertensive, salt-sensitive, and have increased sympathetic tone. Hypertension is also associated with blunted arterial baroreflex sensitivity that can lead to increased cardiovascular risk. Although the endothelin system has been implicated to play a role in baroreflex sensitivity, the role of ET B receptors has not been clearly elucidated. We hypothesized that ET B receptors are necessary for appropriate baroreflex sensitivity. We tested this hypothesis using selective pharmacological blockade of the ET B receptor and using rats that lack functional ET B receptors except in adrenergic tissues (ET B -def rats on WKY background). Anesthetized Sprague-Dawley rats given an intravenous infusion of the ET B receptor antagonist, A-192168 (10 mg/kg), had a blunted heart rate response to phenylephrine-induced pressor ramp compared to post-vehicle baseline (-0.08 ± 0.03 vs. -0.22 ± 0.04 bpm/mmHg; p = 0.048, n = 4). Similarly, anesthetized ET B -def rats had a blunted heart rate response to phenylephrine compared to transgenic controls (0.21 ± 0.07 vs. -0.18 ± 0.04 bpm/mmHg; p = 0.001, n = 3-6/group). ET B -def and transgenic control rats were instrumented with telemetry transmitters (HD-S10 Data Sciences), and mean arterial pressure was recorded for 24 hours and analyzed in 10 second bins. ET B -def rats (n = 6) displayed a significantly higher blood pressure lability compared to transgenic controls (n = 5) as shown by a higher standard deviation of mean arterial blood pressure (11.6 ± 0.2 vs 9.7 ± 0.2 mmHg; p < 0.001) and a greater range of mean arterial blood pressure (85.3 ± 4.0 vs. 68.4 ± 3.6 mmHg; p = 0.01). This increased lability of blood pressure in conscious ET B -def rats is consistent with baroreflex dysfunction. These data support the hypothesis that ET B receptors are integral for appropriate heart rate baroreflex function.