Cardiorespiratory response patterns elicited by microinjections of neuropeptide Y in the nucleus tractus solitarius

Abstract

A limited occipital craniotomy was conducted on anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of neuropeptide Y (NPY), a putative neuromodulator associated with catecholaminergic (CA) synapses, were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the posterior portion of the area postrema, an area of the NTS in which there is known to be a functional coexistence of cardiovascular and respiratory-related neuronal elements. This region of the caudal NTS in the rat is not only the principal site of termination of baro- and chemoreceptor afferents, but it also has profuse reciprocal connections with NPY-containing Cardiorespiratory control regions in the hypothalamus and with other brainstem regulatory nuclei. Moreover, this same region of the rat NTS also shows very high densities of NPY binding sites. Cardiorespiratory responses were subsequently recorded for a 60-min test period following NPY administration. Microinjections of NPY, in the dose range of 10–100 pmol/rat, into the caudal NTS of intact rats produced significant dose-related reductions in mean arterial blood pressure, pulse pressure and minute volume. To a lesser extent, NPY microinjections also produced significant reductions in heart rate, respiratory rate and tidal volume. In a series of separate experiments, in an effort to ascertain the modulatory influences of rostral brain regions on these NPY-evoked, NTS-mediated Cardiorespiratory response patterns, microinjections of NPY were made under identical anesthetic and experimental conditions in a group of rats wherein reciprocal connections between the NTS and rostral brain regions had been disrupted via supracollicular decerebration. In addition, since NPY microinjections were made into specific loci wherein afferent inputs from cardiopulmonary receptors are known to converge in the rat NTS, the effects of bilateral vagotomy on NPY-evoked, NTS-mediated Cardiorespiratory response patterns were also examined in otherwise intact rats and under the same experimental conditions. The effects of NPY microinjections at the same dosage on NTS-mediated Cardiorespiratory response patterns were subsequently compared among the intact, decerebrate and vagotomized rats. The results showed that whereas the hypotensive actions of NPY were not affected by decerebration, vagotomy significantly increased the magnitude of the hypotension elicited by NPY microinjections in comparison to the intact and decerebrate groups of rats. On the other hand, vagotomy abolished the NPY-evoked bradycardia which had a similar magnitude in both intact and decerebrate rats. Similarly, the magnitude of the reduction in respiratory rate was significantly increased in the vagotomized group whereas the hypopnea elicited by NPY was attenuated in the decerebrate group in comparison to intact rats. Further, the NPY-elicited reductions in tidal volume were also abolished in the vagotomized group in comparison to the intact and decerebrate rats. Thus, the data show that NPY microinjections into the medial region of the caudal NTS of intact rats elicited pronounced Cardiorespiratory responses. Disruption of reciprocal connections between the NTS and rostral brain regions via decerebration did not significantly modify the Cardiorespiratory responses elicited by NPY in intact rats, whereas vagotomy markedly affected these NPY-evoked, NTS-mediated Cardiorespiratory response patterns. Overall, the results suggest that NPY may play a physiological role in Cardiorespiratory regulation by modulating CA function within the intrinsic CA/NPY co-storing neuronal systems of the brainstem. Conversely, it is unlikely that the NPY-containing neuronal systems in rostral brain regions such as the hypothalamus necessarily play a crucial role in NPY-evoked, NTS-mediated brainstem mechanisms involved in Cardiorespiratory control.