Cardiac vanilloid receptor 1-expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats - PubMed (original) (raw)

Cardiac vanilloid receptor 1-expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats

Matthew R Zahner et al. J Physiol. 2003.

Abstract

Myocardial ischaemia causes the release of metabolites such as bradykinin, which stimulates cardiac sensory receptors to evoke a sympathoexcitatory reflex. However, the molecular identity of the afferent neurons and fibres mediating this reflex response is not clear. In this study, we tested the hypothesis that the cardiogenic sympathoexcitatory reflex is mediated by capsaicin-sensitive afferent fibres. Enhanced immunofluorescence labelling revealed that vanilloid receptor 1 (VR1)-containing afferent nerve fibres were present on the epicardial surface of the rat heart. Resiniferatoxin (RTX), a potent analogue of capsaicin, was used to deplete capsaicin-sensitive afferent fibres in rats. Depletion of these fibres was confirmed by a substantial reduction of VR1 immunoreactivity in the epicardium and dorsal root ganglia. The thermal sensitivity was also diminished in RTX-treated rats. Renal sympathetic nerve activity (RSNA) and blood pressure were recorded in anaesthetized rats during epicardial application of bradykinin or capsaicin. In vehicle-treated rats, epicardial bradykinin (10 microg ml-1) or capsaicin (10 microg ml-1) application produced a significant increase in RSNA and arterial blood pressure. The RSNA and blood pressure responses caused by bradykinin and capsaicin were completely abolished in RTX-treated rats. Furthermore, epicardial application of iodo-RTX, a highly specific antagonist of VR1 receptors, blocked capsaicin- but not bradykinin-induced sympathoexcitatory responses. Thus, these data provide important histological and functional evidence that the heart is innervated by VR1-expressing afferent nerves and these afferent nerves are essential for the cardiogenic sympathoexcitatory reflex during myocardial ischaemia.

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Figures

Figure 1

Figure 1

Mean paw withdrawal latency in response to a radiant heat stimulus before and 5 days after RTX (200 μg kg−1, n = 14) or vehicle (n = 18) treatment. Data are presented as means ±

s.e.m

. *P < 0.05 compared with baseline values.

Figure 2

Figure 2

Confocal images showing immunofluorescence labelling of VR1 receptors in the left ventricle of the heart (scale bars: 15 μm in A and B) and thoracic dorsal root ganglia (DRG, scale bars: 30 μm in C and D) in a vehicle-treated (Control) and an RTX-treated rat. Note the dense VR1 immunofluorescence on the epicardial surface of the heart in the control rat.

Figure 4

Figure 4

Group data showing the RSNA (A) and mean arterial pressure (MAP, B) responses to epicardial application of bradykinin (10 μg ml−1, n = 10) and capsaicin (10 μg ml−1, n = 9). RSNA responses evoked by bradykinin and capsaicin were measured as the percentage change from baseline RSNA prior to bradykinin application. Data are presented as means ±

s.e.m

. *P < 0.05 compared with respective controls.

Figure 3

Figure 3

Original tracings from a vehicle-treated rat showing RSNA and blood pressure responses to epicardial application of bradykinin (BK, 10 μg ml−1) and capsaicin (CAP, 10 μg ml−1). Bradykinin or capsaicin was applied at the time points indicated by the arrows.

Figure 6

Figure 6

Group data showing RSNA (A) and mean arterial pressure (MAP, B) responses to epicardial application of bradykinin (10 μg ml−1, n = 9) and capsaicin (10 μg ml−1, n = 9). RSNA responses evoked by bradykinin and capsaicin were measured as the percentage change from baseline RSNA prior to bradykinin application. Data are presented as means ±

s.e.m

.

Figure 5

Figure 5

Original tracings showing lack of RSNA and blood pressure responses to epicardial application of bradykinin (BK, 10 μg ml−1) and capsaicin (CAP, 10 μg ml−1) in an RTX-treated rat. Intracerebroventricular bicuculline (BIC, 10 μg in 10 μl vehicle) injection increased blood pressure and RSNA. Bradykinin or capsaicin was applied at the time points indicated by the arrows.

Figure 8

Figure 8

Group data showing RSNA (A) and mean arterial pressure (MAP, B) responses to epicardial bradykinin (10 μg ml−1) plus vehicle or iodo-RTX (200 μ

m

), and capsaicin (10 μg ml−1) plus iodo-RTX in 7 normal control rats. The RSNA following bradykinin or capsaicin application is presented as the percentage change from baseline RSNA. Data are presented as means ±

s.e.m

. *P < 0.05 compared with respective controls.

Figure 7

Figure 7

Original tracings showing the responses of RSNA and arterial blood pressure to epicardial application of vehicle, capsaicin (10 μg ml−1) and bradykinin (10 μg ml−1) in the presence of iodo-RTX (200 μ

m

) in a normal rat. Bradykinin or capsaicin was applied at the time points indicated by the arrows.

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