Distribution of neurons projecting to the rostral ventrolateral medullary pressor region that are activated by sustained hypotension.

Hypotension produces a reflex increase in the activity of sympathetic vasomotor and cardiac nerves. It is believed that the reflex sympathoexcitation is due largely to disinhibition of sympathoexcitatory neurons in the rostral ventrolateral medulla, but it is possible that it may also be mediated by excitatory inputs from interneurons that are activated by a fall in blood pressure. The aim of this study in conscious rabbits was to identify and map neurons with properties that are characteristic of interneurons conveying excitatory inputs to the rostral ventrolateral medullary pressor region in response to hypotension. In a preliminary operation, a retrogradely-transported tracer, fluorescent-labelled microspheres, was injected into the functionally-identified pressor region in the rostral ventrolateral medulla. After a waiting period of at least one week, a moderate hypotension (decrease in arterial pressure of approximately 20 mmHg) was induced in conscious rabbits for 60 min by the continuous infusion of sodium nitroprusside. In confirmation of a previous study from our laboratory, [Li and Dampney (1994) Neuroscience 61, 613634] hypotension resulted in the expression of Fos (the protein product of c-fos, a marker of neuronal activation) in many neurons in several distinct regions in the brainstem and hypothalamus. Some of these regions (nucleus tractus solitarius, area postrema, caudal and intermediate ventrolateral medulla, parabrachial complex in the pons, and paraventricular nucleus in the hypothalamus) also contained large numbers of retrogradely-labelled cells. Approximately 10% of the Fos-positive neurons in the nucleus tractus solitarius, and 15-20% of Fos-positive neurons in the caudal and intermediate ventrolateral medulla were also retrogradely-labelled from the rostral ventrolateral medullary pressor region. In other brain regions, very few double-labelled neurons were found. In previous studies from our laboratory, we have determined the distribution of neurons in the brainstem that project to the rostral ventrolateral medullary pressor region and that are also activated by hypertension [Polson et al. (1995) Neuroscience 67, 107-123] or by hypoxia. [Hirooka et al. (1997) Neuroscience 80, 1209-1224] Comparison of the present results with those from these previous studies indicate that although hypotension and hypoxia both elicit powerful reflex sympathoexcitatory responses, the central pathways subserving these effects in conscious animals are fundamentally different. Hypoxia activates rostral ventrolateral medullary sympathoexcitatory neurons mainly via a major direct excitatory projection from the nucleus tractus solitarius, as well as from the Kölliker-Fuse nucleus in the pons, while in contrast the activation of these neurons in response to hypotension appears to be due mainly to disinhibition, mediated via inhibitory interneurons. In addition, however, inputs originating from excitatory interneurons in the nucleus tractus solitarius and caudal and intermediate parts of the ventrolateral medulla appear to contribute to the hypotension-evoked activation of sympathoexcitatory neurons in the rostral ventrolateral medulla.