Oral Presentation Neuropathophysiology - an ISH satellite 2012

Carotid sinus nerve ablation in adult spontaneously hypertensive rats (SHR) is chronically anti-hypertensive and sympathoinhibitory: a direct telemetric investigation (#47)

Fiona D McBryde 1 , Ana P L Abdala 1 , Emma B Hendy 1 , Angus K Nightingale 2 , Paul A Sobotka 3 , Zoar Engelman 3 , Julian F R Paton 1
  1. Univeristy of Bristol, Bristol, UK, United Kingdom
  2. Department of Cardiology, Bristol Heart Institute, Bristol Royal Infirmary, Bristol, UK
  3. Coridea NCI, New York, New York 10001, USA

Objectives: In both hypertensive patients1 and SHR2 the peripheral chemoreflex is hyper-sensitive. Whether peripheral chemoreceptors provide a tonic excitatory drive that contributes to the sympathetic over-activation and high arterial pressure (AP) is unknown. We have previously shown that carotid sinus denervation (CSD) in young pre-hypertensive SHR ameliorates the development of hypertension3. In this study, we tested the hypothesis that CSD would lower AP and sympathetic activity (SNA) in adult SHR with established hypertension.

Methods and Results: In 12 week-old SHR previously instrumented to record AP telemetrically, bilateral CSD (n=7) or Sham surgery (n=6) and jugular catheterisation were performed on Day 0. Chemoreflex elimination was confirmed by intravenous injection of sodium cyanide (120μg.kg-1; Sham +15±3mmHg, CSD +1±2mmHg) on Day 7. Following CSD, systolic AP showed a sustained (>28 days) reduction, of -15±1 mmHg from a baseline of 160±8 mmHg (p<0.05); Sham rats increased systolic AP by +4±3mmHg. The reductions in the depressor response to ganglionic blockade (hexamethonium 10mg.kg-1; -4±7 vs. -24±5 mmHg, CSD vs Sham) and low frequency power of systolic AP (-0.8±0.1mmHg2 p<0.05) indicate sympathoinhibition. This was confirmed with direct telemetric recordings (n=3), where CSD reduced renal SNA by 57±9% at Day 14. Renal nerve viability was confirmed by brief exposure to high frequency noise stress (139±28% Day -3; 152±9% Day 14). Baroreceptor reflex evaluation with intravenous vasoactive drug infusions revealed a partial resetting of both the cardiac and renal sympathetic baroreflex curves. 

Conclusions: CSD reduces AP in adult SHR associated with a pronounced reduction in sympathetic drive and improved cardiac baroreflex sensitivity. This finding supports the notion that the peripheral chemoreflex is sensitised in the SHR and provides tonic afferent drive contributing to the maintenance of hypertension.

  1. Trzebski A, Tafil M, Zoltowski M, Przybylski J. Increased sensitivity of the arterial chemoreceptor drive in young men with mild hypertension. Cardiovasc Res 1982 Mar;16(3):163-72.
  2. Tan ZY, Lu Y, Whiteis CA, Simms AE, Paton JF, Chapleau MW, et al. Chemoreceptor hypersensitivity, sympathetic excitation, and overexpression of ASIC and TASK channels before the onset of hypertension in SHR. Circ Res 2010;106(3):536-45.
  3. Abdala AP*, McBryde FD*, Marina N, Hendy EB, Engelman Z, Fudim M, Sobotka PA, Gourine A, Paton J. Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat. J Physiol. 2012 Jun 11. [Epub ahead of print]