Carotid sinus denervation (CSD) ameliorates renovascular hypertension in adult Wistar rats

Abstract

The peripheral chemoreflex is known to be hyper-responsive in both spontaneously hypertensive (SHR) and Goldblatt hypertensive (2 kidney 1 clip; 2K1C) rats. We have previously shown that carotid sinus nerve denervation (CSD) reduces arterial blood pressure (ABP) in SHR. Here, we show that CSD ameliorates 2K1C hypertension and reveal potential underlying mechanisms. Adult Wistar rats were instrumented to record ABP via telemetry, then underwent CSD (n = 9) or sham CSD (n = 9) five weeks after renal artery clipping, versus normal Wistar (n = 5). After 21 days renal function was assessed, and tissue collected to assess sympathetic postganglionic intracellular calcium transients ([Ca²⁺]_i) and immune cell infiltrates. Hypertensive 2K1C rats showed a profound elevation in ABP (Wistar: 98 ± 4 mmHg vs. 2K1C: 147 ± 8 mmHg; P < 0.001), coupled with impairments in renal function and baroreflex sensitivity, increased neuro-inflammatory markers and enhanced [Ca²⁺]_I in stellate neurons (P < 0.05). CSD reduced ABP in 2K1C+CSD rats and prevented the further progressive increase in ABP seen in 2K1C+sham CSD rats, with a between-group difference of 14 ± 2 mmHg by Week 3 (P < 0.01), accompanied by improvements in both baroreflex control and spectral indicators of cardiac sympatho-vagal balance. Furthermore, CSD improved protein and albuminuria, decreased [Ca²⁺]_i evoked responses from stellate neurons, and reduced indicators of brainstem inflammation. In summary, CSD in 2K1C rats reduces the hypertensive burden and improves renal function. This may be mediated by improvements in autonomic balance, functional remodelling of post-ganglionic neurones and reduced inflammation. Our results suggest that the peripheral chemoreflex may be considered as a potential therapeutic target for controlling renovascular hypertension.

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