Abstract:
We have shown recently that carotid sinus denervation (CSD) reduced arterial pressure (AP) in spontaneously hypertensive rats (SHR) but was without effect in normotensive Wistar rats. It remains unknown whether this anti-hypertensive effect is specific to the SHR. However, since the peripheral chemoreflex is sensitised in the Goldblatt (2 kidney, 1 clip; 2K1C) renovascular hypertensive model, we have tested whether established 2K-1C hypertension can be ameliorated by CSD. Under ketamine/medetomidine anaesthesia (75mg/kg + 0.5mg/kg, IP), the left renal artery of 6 week old Wistar rats was partially occluded with a silver clip. At 11 weeks of age, rats were instrumented to record AP telemetrically, and after a 7 day baseline recording underwent CSD or Sham surgery. Prior to CSD/Sham surgery, AP rose steadily during baseline at 1.0±0.5 mmHg/day. This continued in Sham (+1.3±1.0 mmHg/day) but not CSD (-0.3±0.9 mmHg/day). Thus, at 14 weeks of age AP was unchanged from baseline in CSD rats (183±16 vs. 182±17 mmHg), but had continued to increase in Sham rats (201±18 vs. 210±21mmHg). Spontaneous baroreflex gain increased in CSD (-1.16±0.16 vs. -1.25±0.15 bpm/mmHg) but not Sham (1.1±0.09 vs. 1.0±0.12 bpm/mmHg). Reductions in low (6.3±0.5 vs. 6.0±0.8 mmHg2) and very low frequency (2.8±0.5 vs. 1.8±0.2 mmHg2) spectral power of systolic AP were seen in CSD but not Sham, suggesting sympathoinhibition. In addition, we have observed a reduction in macrophage infiltration in the brainstem after CSD in 2K1C rats, a response not observed in Sham animals. Using metabolic cages, we are now assessing any alterations of CSD on renal function in 2K1C rats and comparing with a Sham group. Preliminary data indicate that CSD improves glomerular filtration rate. We will present these data in full at the meeting. In conclusion, CSD appears to stunt the continued increase AP in 2K-1C rat. The mechanisms for this include: sympathoinhibition, improved baroreflex gain and renal function as well as reduced systemic inflammation. Where applicable, experiments conform with Society ethical requirements.
