Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC22
Peripheral chemoreceptor inputs contribute to the development of high blood pressure in spontaneously hypertensive rats
A. Abdala1, N. Marina2, A. Gourine2, J. Paton1
1. University of Bristol, Bristol, United Kingdom. 2. University College London, London, United Kingdom.
The peripheral chemoreceptor (PC) reflex is enhanced in subjects with hypertension (Trzebski et al. 1982). In the spontaneously hypertensive rat (SHR), carotid body glomus cells from juvenile SHR show hypersensitivity to acidosis even before the onset of hypertension (Tan et al. 2010). Furthermore, pre-hypertensive SHRs (PH-SHR) display enhanced sympathoexcitatory responses to PC stimulation (Tan et al. 2010). We hypothesized that heightened PC activity in PH-SHR contributes to the development of hypertension in this rodent model of neurogenic hypertension in later life and that this is caused by pro-inflammatory cytokines resident in the carotid body of the PH-SHR. All procedures conformed to the UK Home Office guidelines on animals (Scientific Procedures) Act 1986 and were approved by the University of Bristol’s Animal Ethic Committee. In 4-5 week PH-SHR (n=7) and age- and sex- matched Wistar rats (n=7) the carotid body was ablated under general anaesthesia (ketamine 60 mg.kg-1 with metedomidine 0.25 mg.kg-1 i.p.); depth of anaesthesia was assessed by the absence of a withdrawal response to a noxious pinch to the tail. Sham operated rats were also prepared (PH-SHR and WKY; 4-5 weeks old; n=7 each). One day after the surgery all animals with carotid body ablation failed to respond to hypoxia (10% O2) confirming full excision. Five days prior to measurement of arterial pressure (AP), when rats were 12 weeks old, all animals (carotid ablated and sham) were re-anaesthetised (Halothane, 3% in oxygen) and a catheter was inserted into the femoral artery to measure arterial pressure chronically from conscious, freely moving animals. Adult carotid body excised SHRs (12 weeks) showed lower mean AP than sham operated SHRs (121±3 vs 145±10 mmHg, mean ± SEM, ANOVA, SNK, P<0.05). The mean AP of SHR with carotid body ablation remained significantly higher than both Wistar control groups (SHAM 95±3 mmHg, carotid body excised 101±3 mmHg, P<0.05). Immunohistochemical analysis of carotid bodies from sham SHRs revealed strong expression of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), IL-1β receptor I and TNF-α-receptor II in tyrosine hydroxilase-positive glomus cells type 1. In conclusion, carotid body excision in juvenile PH-SHR reduces the degree of hypertension in later adult life. We suggest that PC hypersensitivity induced by chronic inflammation contributes to the development of high sympathetic drive and concomitant hypertension in the SHR.
Where applicable, experiments conform with Society ethical requirements