Pronounced reduction in parasympathetic innervation of brainstem vasculature in pre-hypertensive SHR rats

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, PC197

Poster Communications: Pronounced reduction in parasympathetic innervation of brainstem vasculature in pre-hypertensive SHR rats

E. Roloff1, J. R. Paton1

1. Physiology and pharmacology, University of Bristol, Bristol, United Kingdom.

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Hypertension is a growing clinical problem. Understanding its aetiology could provide exciting new avenues for treatment and prevention. In humans and animals models, such as the Spontaneous Hypertensive Rat (SHR), it is commonly associated with high levels of sympathetic activity. Recent findings describe vertebrobasilar artery remodelling (wall thickening & lumen narrowing) in SHRs that occurs before the hypertension develops1. We hypothesise this may be caused by increased sympathetic or decreased parasympathetic innervation of vertebrobasilar arteries. Thus, we examined these vessels in SH and Wistar-Kyoto (WKY) (normotensive) rats with focus on any changes in innervation that occurred with age and the development of hypertension in the SHR. We used 7 pre-hypertensive (4-5w old) and 8 hypertensive (adult) SHRs and compared them to age-matched WKYs (N=4 and 8, respectively), all male. Rats were euthanised with sodium pentobarbital (200mg/ml) and transcardially perfused with 4% PFA. Ventral brainstem meninges containing the main vasculature were labelled with the sympathetic noradrenergic marker αDBH and parasympathetic cholinergic marker αVAChT. Images from the Vertebral Arteries (VA), Basilar Artery posteriorly (BAp) & Basilar Artery anteriorly (BAa) were sampled using fluorescent microscopy. For each the number of DBH or VAChT stained fibres was summated within 3 ‘regions of interest’ (0.15×0.15mm). Fibre densities were calculated as fibres/(100µm)2±SEMs. 2way-ANOVAs and post-hoc Bonferronis (BFs) statistical tests were employed. The biggest difference was observed in the parasympathetic innervation of SHRs compared to WKYs. Lower densities (-75%) occurred in both young (WKYs: 3.8-4.6 and SHRs: 1.0-1.3 (±0.1-0.6)) and adult rats (WKYs: 3.2-4.3 and SHRs: 0.6-1.1 (±0.2-0.8)) and hence was irrespective of hypertension. The effect was highly significant for both ages (ps<0.0001). All 3 areas were affected (0.001>ps<0.05, BF). Sympathetic fibre densities were almost double that of the parasympathetic system, but the differences observed were more modest. Again SHRs had lower fibre densities than WKYs in both young (WKYs: 5.3-9.1 and SHRs: 4.9-5.3 (±0.4-1.2)) and adults (WKYs: 5.0-6.8 and SHRs: 3.3-4.6 (±0.5-0.8)). The effect was significant for both ages (p<0.05 and p<0.0001 respectively). Vessel position was also significant in young (p<0.01). At both ages the BAp was significant in the BF (ps 0.05 and 0.01 respectively) so was the VA in adults (p<0.05). Parasympathetic fibres mostly ran parallel to the sympathetic fibres. We conclude that there is a paucity of parasympathetic innervation to the vertebrobasilar circulation and that this is present from early life in SHR. Given this finding, we propose that autonomically mediated vasodilatation of the vertebrobasilar arteries will be compromised in the SHR.



Where applicable, experiments conform with Society ethical requirements.

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