Carotid Sinus Nerve Ablation in Adult Spontaneously Hypertensive Rats (Shr) Is Chronically Anti-Hypertensive

Abstract

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 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 catheterization were performed on Day 0. Chemoreflex elimination was confirmed by intravenous injection of sodium cyanide (120 [mu]g.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. CSD rats showed a reduced depressor response to ganglionic blockade (hexamethonium 10 mg.kg-1; -4 +/- 7 vs. -24 +/- 5 mmHg, CSD vs Sham) and a fall in low frequency power of systolic AP (-0.8 +/- 0.1mmHg2 p < 0.05). Cardiac baroreflex evaluation with intravenous vasoactive drug infusions revealed a shift in the operating-point of heart rate to the centre of the linear part of the curve after CSD. Conclusions: CSD reduces AP in adult SHR associated with a reduction in global sympathetic drive and improved 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. Ana P.L. Abdala, Julian F. R. Paton, and Alexander V. Gourine. Peripheral chemoreceptor inputs contribute to the development of high blood pressure in spontaneously hypertensive rats. FASEB J 2011 25:640.10