Carotid sinus denervation 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 (two kidney one clip; 2K1C) rats. We have previously shown that carotid sinus nerve denervation (CSD) reduces arterial blood pressure (ABP) in SHR. In the present study, we show that CSD ameliorates 2K1C hypertension and reveal the potential underlying mechanisms. Adult Wistar rats were instrumented to record ABP via telemetry, and then underwent CSD (n = 9) or sham CSD (n = 9) 5 weeks after renal artery clipping, in comparison with normal Wistar rats (n = 5). After 21 days, renal function was assessed, and tissue was collected to assess sympathetic postganglionic intracellular calcium transients ([Ca ] ) 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 neuroinflammatory markers and enhanced [Ca ] 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), which was accompanied by improvements in both baroreflex control and spectral indicators of cardiac sympatho-vagal balance. Furthermore, CSD improved protein and albuminuria, decreased [Ca ] evoked responses from stellate neurons, and also 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 neurons and reduced inflammation. Our results suggest that the peripheral chemoreflex may be considered as a potential therapeutic target for controlling renovascular hypertension.

Aberrant reflex mechanisms contributing to reno‐vascular hypertension: a pain in the neck?

“…The incomplete recovery of arterial pressure observed by Pijacka et al . () is consistent with this finding. Thus reductions in SNA per se are probably not sufficient to completely reverse the elevations in arterial pressure without reversal of stenosis and restoration of renal blood flow.…”

“…The findings of Pijacka et al . () indicate that CSD is an effective means of reducing arterial pressure and improving autonomic balance in the 2K1C model. Reduced afferent activation of autonomic nuclei in the brainstem, as well as decreased reflex increases in renal SNA, and subsequent reduction of RAAS activation and kidney damage, could account for the improvements in arterial pressure.…”

Translating carotid body function into clinical medicine

“…), Goldblatt hypertension (Pijacka et al . ) and spontaneous hypertension (Abdala et al . ); (2) reduced the breathing instability, the enhanced sympathetic activity and improved the survival rate in animal models of HF (Del Rio et al .…”

Interdependent feedback regulation of breathing by the carotid bodies and the retrotrapezoid nucleus

“…; Pijacka et al . ,b). This hyperactivity is not driven by a change in arterial blood gases and contributes to the pathogenic increase in sympathetic nerve activity present in these human diseases and their animal models (Pijacka et al .…”

“…As suggested previously (Pijacka et al . ), SNA may remain chronically elevated because of a reduction in the baroreflex. Also, because resting breathing is unchanged in OSA and hypertension, we also suggest that the emphasis on cardiorespiratory coupling as the underlying cause of the increased SNA may be exaggerated and that the role of pathways that directly link carotid body afferents to the vasomotor presympathetic neurons of the RVLM should be further evaluated.…”