We have reported that noxious pinch attenuates the cardiac baroreflex (Boscan et al. 2002). This nociceptive attenuation of the baroreflex bradycardia is blocked by NK-1 receptor antagonists and mimicked by substance P (SP) microinjected to the nucleus of the solitary tract (NTS). Here, we examine the effect of noxious pinch and NTS microinjections of SP on baroreflex sympathoinhibition.
Using a novel variant of the working heart-brainstem preparation (WHBP; Paton, 1996), a decerebrated (under halothane anaesthesia) artificially perfused rat, sympathetic nerve activity was recorded from the lumbar (L2-3) and thoracic chain (T8-9), and the adrenal nerve. In the WHBP, cardiac sympathetic and vagal branches were also recorded. Noxious stimuli were delivered to the paw with a calibrated mechanical pincher. Data are means ± S.E.M. and Student’s paired t test was used.
Sympathetic nerve activity showed respiratory modulation, peaking during early post-inspiration. Perfusion pressure ramps demonstrated baroreflex sympathoinhibition in all outflows. Hindlimb pinch evoked increases in sympathetic activity (212 ± 32 %, n = 6), accompanied by increased pressure (8 ± 2 mmHg), tachycardia (8 ± 2 b.p.m.) and tachypnoea (192 ± 27 %). Noxious pinch attenuated the cardiac vagal baroreflex gain (-1.71 to -0.74 b.p.m. mmHg-1, P < 0.01, n = 6). In contrast, the baroreflex sympathoinhibition was unaffected (-69 ± 4 vs. -77 ± 6 %).
NTS microinjection of SP (0.5 pmol, 50 nl) produced a reversible inhibition of cardiac baroreflex gain (-1.81 to -0.68 b.p.m. mmHg-1, P < 0.005, n = 6) but no change in the baroreflex sympathoinhibition (-78 ± 4 vs. -76 ± 6 %). Recordings from the inferior cardiac nerve showed a similar lack of effect of SP on baroreflex sympathoinhibition. However, baroreflex-evoked activity on the cardiac vagal nerve was attenuated by SP. No change was seen in the baroreflex sympathoinhibition at doses of SP up to 50 pmol even when microinjected at two rostro-caudally distinct sites bilaterally within the NTS. By comparison microinjection of the GABAA agonist (isoguvacine, 500 pmol, 50 nl) reversibly attenuated both components of the baroreflex.
These data indicate that noxious pinch and SP selectively modulate the vagal component of the baroreflex by an action within the NTS. Further this implies that there are distinct and differentially regulated baroreflex pathways with outputs to the para- and sympathetic nervous systems within the NTS.
This work was funded by RCA/BJA and BHF.