Direct projections from the cardiovascular nucleus tractus solitarii to pontine preganglionic parasympathetic neurons: A link to cerebrovascular regulation

Abstract

Peripheral or central interruption of the baroreflex or the parasympathetic innervation of cerebral vessels leads to similar changes in regulation of cerebral blood flow. Therefore, we sought to test the hypothesis that the cardiovascular nucleus tractus solitarii, the site of termination of arterial baroreceptor nerves, projects to pontine preganglionic neurons whose stimulation elicits cerebral vasodilatation. The current study utilized both light and electron microscopic techniques to analyze anterograde tracing from the cardiovascular nucleus tractus solitarii to preganglionic parasympathetic neurons in the pons. We further used retrograde tracing from that same pontine region to the cardiovascular nucleus tractus solitarii and evaluated the confluence of tracing from the cardiovascular nucleus tractus solitarii to pontine preganglionic neurons labeled retrogradely from the pterygopalatine ganglia. The cardiovascular nucleus tractus solitarii projected to pontine preganglionic parasympathetic neurons, but more rostral and caudal regions of nucleus tractus solitarii did not. In contrast, all three regions of nucleus tractus solitarii projected to the nucleus ambiguus and dorsal motor nucleus of the vagus. Although not projecting to pontine preganglionic parasympathetic neurons, regions lateral, rostral, and caudal to cardiovascular nucleus tractus solitarii sent projections through the pons medial to the preganglionics. The study establishes the presence of a direct monosynaptic pathway from neurons in the cardiovascular nucleus tractus solitarii to pontine preganglionic parasympathetic neurons that project to the pterygopalatine ganglia, the source of nitroxidergic vasodilatory innervation of cerebral blood vessels. It provides evidence that activation of those preganglionic neurons can cause cerebral vasodilatation and increased cerebral blood flow. Finally, it demonstrates differential innervation of medullary and pontine preganglionic parasympathetic neurons by different regions of the nucleus tractus solitarii.

Neuronal nitric oxide mediates cerebral vasodilatation during acute hypertension

“…Stimulation of those ganglia leads to cerebral arterial dilatation (Seylaz, J. et al, 1988;Toda, N. et al, 2000b;Toda, N. et al, 2000a) and some reports, which indicate that interruption of the ganglia or their innervation leads to cerebral vasoconstriction (Toda, N. et al, 2000b;Toda, N. et al, 2000a), suggest that they exert a tonic vasodilator influence. Stimulation of the superior salivatory nucleus (SSN), the site of preganglionic neurons that project to the pterygopalatine ganglia and thus influence CBF, also leads to vasodilatation of cerebral vessels (Agassandian, K. et al, 2002). Ganglionic neurons of the pterygopalatine ganglia express a number of potentially vasoactive substances including vasoactive intestinal polypeptide, ACh (implied by the presence of choline acetyltransferase), and nNOS, which would synthesize NO (Yu, J. G. et al, 1998).…”

“…Our own laboratory has suggested that the pathway may contribute to cerebral vasodilatation during hypertension and thus extend cerebrovascular autoregulation (Talman, W. T. et al, 1994), a suggestion that has been echoed by others in the field (Toda, N. and Okamura, T., 1992). We have shown that arterial baroreceptors are critical for cerebral vasodilatation when blood pressure has been raised beyond the autoregulatory range (Talman, W. T. et al, 1994;Talman, W. T. and Nitschke Dragon, D., 1995b;Talman, W. T. and Nitschke Dragon, D., 2002); that the NTS, where arterial baroreceptor fibers terminate in the central nervous system (Blessing, W. W. et al, 1999;Ciriello, J., 1983;Kalia, M. and Sullivan, J. M., 1982;Torrealba, F. and Claps, A., 1988), projects directly to the SSN (Agassandian, K. et al, 2002); that interruption of function at the level of SSN or pterygopalatine ganglia extends the autoregulatory range during hypertension as does baroreflex interruption (Agassandian, K. et al, 2003;Talman, W. T. and Nitschke Dragon, D., 2000), and that non-selective inhibition of synthesis of NO released by those ganglionic fibers had the same effect (Talman, W. T. and Nitschke Dragon, D., 1995a). These studies further suggest that nitroxidergic nerves projecting from the pterygopalatine ganglion to cerebral blood vessels play a roll in the increase in CBF seen in breakthrough (Talman, W. T. and Nitschke Dragon, D., 2000).…”

“…However, when AP exceeds an upper limit, breakthrough of autoregulation occurs, cerebral blood vessels dilate, and CBF increases dramatically (MacKenzie, E. T. et al, 1976;Skinhoj, E. and Strandgaard, S., 1973). We have found that breakthrough may be delayed to much higher blood pressures if the arterial baroreflex is interrupted either peripherally or centrally (Talman, W. T. et al, 1994;Talman, W. T. and Nitschke Dragon, D., 2002) and we recently showed that baroreceptor pathways through the nucleus tractus solitarii project directly to preganglionic parasympathetic neurons that themselves influence CBF (Agassandian, K. et al, 2002;Agassandian, K. et al, 2003). As when the baroreflex is interrupted, breakthrough is also attenuated, and the breakthrough point shifted to higher AP's, when the nitroxidergic innervation to the cerebral vessels is interrupted (Talman, W. T. and Nitschke Dragon, D., 2000) or when nitric oxide (NO) synthesis is inhibited by systemic administration of a nonselective NO synthase (NOS) inhibitor (Talman, W. T. and Nitschke Dragon, D., 1995a).…”

Blunted cerebral blood flow velocity in response to a nitric oxide donor in postural tachycardia syndrome

“…Agassandian et al (1) and Boysen et al (4) have shown that direct projections from the cardiovascular nucleus tractus solitarii to the pontine preganglionic parasympathetic neurons, acting through the pterygopalantine ganglia, provide tonic dilatory influences on the cerebral vessels. This may provide a link between changes in central blood volume and arterial baroreflexes to influence cerebral vascular regulation via the extrinsic vascular innervation system (15).…”

Vestibular effects on cerebral blood flow

“…Connection have been found between the Vestibular Nuclei and the Fastigial Nucleus, 2 then to the Rostral Ventrolateral Medulla, 3 followed by vasodilatory connections to the cerebral vessels. 4 Similarly, neurons travel from the Vestibular Nuclei to the Nucleus Tractus Solitarius 5 and then to the Pterygopalatine Ganglion, 6 resulting in cerebral vasodilation. 7 However, the role these connections play with respect to adjustments to posture remains to be determined.…”