Central pathways in the pons and midbrain involved in cardiac sympathoexcitatory reflexes in cats

Activation of cardiac sympathetic afferents elicits pain and excitatory cardiovascular reflexes including acute hypertension and tachyarrhythmias. Our previous studies have shown that specific regions in the medulla, such as the nucleus of solitary tract and ventrolateral medulla, are involved in central regulation of cardiac sympathoexcitatory reflexes. However, the contributions of supramedullary nuclei to these reflexes have not been characterized. In the present study, we located activated neurons in the pons and midbrain induced by inputs from cardiac sympathetic afferents by detecting their c-Fos immunoreactivity. In anesthetized cats with bilateral carotid denervation and cervical vagotomy, epicardial application of bradykinin (1-10 microg, in 0.1 ml; n=7) was performed on the anterior surface of the left ventricle six times, every 20 min. Repetitive application of bradykinin caused consistent excitatory cardiovascular reflexes characterized by increases in blood pressure and heart rate. No responses were evoked by the vehicle for bradykinin (0.9% saline, n=7). Compared to control cats, c-Fos immunoreactive cells were significantly increased (P<0.05) in the rostral pons, caudal and intermediate midbrain in the bradykinin-treated cats. The specific areas activated include the parabrachial nucleus, Kölliker-Fuse nucleus, locus coeruleus, dorsal nucleus of raphe, and dorsal, lateral and ventrolateral periaqueductal gray. From these results we suggest that cardiovascular-related regions in the pons and midbrain form part of a long loop in central integration of cardiac sympathoexcitatory reflexes.