Abstract 505: Effects of Etamicastat, a Selective Peripheral Dopamine-β-Hydroxylase Inhibitor, Upon Stress-induced Changes in Blood Pressure in the SHR
Stressors induce an overactivation of the sympathetic nervous system (SNS) that triggers several changes in the body as a response to stress. These changes include vasoconstriction and increase in heart rate, which results in raised blood pressure (BP). Etamicastat is a selective dopamine-β-hydroxylase (DβH) inhibitor that decreases norepinephrine levels in peripheral sympathetically innervated tissues.
Cardiovascular parameters were measured after a single oral administration of etamicastat (30 mg/kg) 9 h post-administration in male spontaneously hypertensive rats (SHR) by radio-telemetry or tail-cuff recording. Telemetered recording was performed in both restrained and unrestrained animals.
Etamicastat treatment had no effect on heart rate (HR, beats/min) in any recording method. HR measured in unrestrained SHR instrumented with radio-telemetry probes (305±5) consistently yielded HR values significantly lower than restrained animals (362±11) or those recorded by tail-cuff (393±7). On the other hand, single-dose oral etamicastat treatment decrease in mean arterial pressure (MAP, mm Hg) was -14.0±2.0 from 153.3±4.0 in telemetered unrestrained animals, -26.1±5.1 from 182.8±6.4 in telemetry-implanted restrained SHR and -47.9±7.0 from 183.4±9.5 recorded by tail-cuff method. In addition, a power spectral analysis was performed to evaluate BP variability (BPV), in SHR implanted with radio-telemetry probes, at high frequency (HF: 1-2 Hz), low frequency (LF: 0.2-0.6 Hz) and very low frequency (VLF: 0.02-0.2 Hz). The stressor (i.e., cage restrainement) increased the ratio LF/HF-BPV in untreated SHR from 5.23±1.24 to 10.03±1.75, which results from the activation of the SNS. Treatment with etamicastat decreased the ratio LF/HF-BPV in stressed SHR from 10.03±1.75 to 4.46±0.68 and in non-stressed SHR from 5.23±1.24 to 2.23±0.39.
In conclusion, etamicastat treatment reduces (1) high BP in SHR, (2) the stress-induced increase in SNS drive and (3) the stress-induced increase in BP.
Author Disclosures: B. Igreja: A. Employment; Modest; Bial employee. N. Pires: A. Employment; Modest; Bial employee. L.C. Wright: A. Employment; Modest; Bial employee. P. Soares-da-Silva: None.
- © 2014 by American Heart Association, Inc.