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 vasom otor and cardiac nerves. It is believed that the reflex sympathoexcitation is due largely to disinhibition of sympathoexcitatory neurons in the rostra l 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 ma p neurons with properties that are characteristic of interneurons conveying excitatory inputs to the rostral ventrolateral medullary presser region in response to hypotension. In a preliminary operation, a retrogradely-transp orted tracer, fluorescent-labelled microspheres, was injected into the func tionally-identified presser region in the rostral ventrolateral medulla. Af ter a waiting period of at least one week, a moderate hypotension (decrease in arterial pressure of approximately 20 mmHg) was induced in conscious ra bbits for 60 min by the continuous infusion of sodium nitroprusside. In con firmation of a previous study from our laboratory, [Li and Dampney (1994) N euroscience 61, 613-634] 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 the se regions (nucleus tractus solitarius, area postrema, caudal and intermedi ate ventrolateral medulla, parabrachial complex in the pens, and paraventri cular nucleus in the hypothalamus) also contained large numbers of retrogra dely-labelled cells. Approximately 10% of the Fos-positive neurons in the n ucleus tractus solitarius, and 15-20% of Fos-positive neurons in the caudal and intermediate ventrolateral medulla were also retrogradely-labelled fro m the rostral ventrolateral medullary presser region. In other brain region s, very few double-labelled neurons were found. In previous studies from ou r laboratory, we have determined the distribution of neurons in the brainst em that project to the rostral ventrolateral medullary presser region and t hat are also activated by hypertension [Polson et al. (1995) Neuroscience 6 7, 107-123] or by hypoxia. [Hirooka et nl. (1997) Neuroscience 80, 1209-122 4] 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 effect s in conscious animals are fundamentally different. Hypoxia activates rostr al ventrolateral medullary sympathoexcitatory neurons mainly via a major di rect excitatory projection from the nucleus tractus solitarius, as well as from the Kolliker-Fuse nucleus in the pens, while in contrast the activatio n of these neurons in response to hypotension appears to be due mainly to d isinhibition, mediated via inhibitory interneurons. In addition, however, i nputs originating from excitatory interneurons in the nucleus tractus solit arius and caudal and intermediate parts of the ventrolateral medulla appear to contribute to the hypotension-evoked activation of sympathoexcitatory n eurons in the rostral ventrolateral medulla. (C) 1999 IBRO. Published by El sevier Science Ltd.