Abstract

The rostral ventrolateral medulla (RVLM) contains neurons involved in tonic and reflex control of arterial pressure. We describe the effects of gamma-aminobutyric acid (GABA) and anesthetics injected into the RVLM of conscious and urethane (1.2 g/kg, iv) anesthetized Wistar rats (300-350 g). In conscious rats, bilateral microinjection of GABA (50 nmol/200 nl) induced a small but significant decrease in blood pressure (from 130 +/- 3.6 to 110 +/- 5.6 mmHg, N = 7). A similar response was observed with sodium pentobarbital microinjection (24 nmol/200 nl). However, in the same animals, the fall in blood pressure induced by GABA (from 121 +/- 8.9 to 76 +/- 8.8 mmHg, N = 7) or pentobarbital (from 118 +/- 4.5 to 57 +/- 11.3 mmHg, N = 6) was significantly increased after urethane anesthesia. In contrast, there was no difference between conscious (from 117 +/- 4.1 to 92 +/- 5.9 mmHg, N = 7) and anesthetized rats (from 123 +/- 6.9 to 87 +/- 8.7 mmHg, N = 7) when lidocaine (34 nmol/200 nl) was microinjected into the RVLM. The heart rate variations were not consistent and only eventually reached significance in conscious or anesthetized rats. The right position of pipettes was confirmed by histology and glutamate microinjection into the RVLM. These findings suggest that in conscious animals the RVLM, in association with the other sympathetic premotor neurons, is responsible for the maintenance of sympathetic vasomotor tone during bilateral RVLM inhibition. Activity of one or more of these premotor neurons outside the RVLM can compensate for the effects of RVLM inhibition. In addition, the effects of lidocaine suggest that fibers passing through the RVLM are involved in the maintenance of blood pressure in conscious animals during RVLM inhibition.

Highlights

  • A turning point in our knowledge of the autonomic nervous system control of arterial blood pressure (BP) was the identification of the ventrolateral medulla and the demonstration of its key role in BP maintenance and reflex cardiovascular control [1,2,3].Two distinct areas have been identified within the ventrolateral medulla: the rostral ventrolateral medulla (RVLM), responsible for maintaining the tonic excitation of sympathetic preganglionic neurons [4,5], and the caudal ventrolateral medulla, a depressor area clearly involved in the reflex regulation of BP [2,3]

  • When gamma-aminobutyric acid (GABA) was microinjected into the RVLM in anesthetized animals (N = 7), a significant and prominent decrease in Mean arterial pressure (MAP) was observed but no significant change in heart rate (HR) was observed

  • The major new finding of the present study was the demonstration that: 1) the fall in BP in response to microinjection of GABA and pentobarbital into the RVLM was greater in anesthetized than in conscious animals, and 2) there was no difference between groups when lidocaine was injected

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Summary

Introduction

A turning point in our knowledge of the autonomic nervous system control of arterial blood pressure (BP) was the identification of the ventrolateral medulla and the demonstration of its key role in BP maintenance and reflex cardiovascular control [1,2,3].Two distinct areas have been identified within the ventrolateral medulla: the rostral ventrolateral medulla (RVLM), responsible for maintaining the tonic excitation of sympathetic preganglionic neurons [4,5], and the caudal ventrolateral medulla, a depressor area clearly involved in the reflex regulation of BP [2,3]. Electrolytic lesion or chemical inactivation of RVLM neurons by inhibitory amino acids such as glycine or gamma-aminobutyric acid (GABA) results in a fall of BP similar to that usually obtained in acute spinal animals [4,10,11,12]. These studies were performed on anesthetized animals, a condition that may be a limiting factor in the interpretation and analysis of the results. There is no comparative study regarding the cardiovascular effects of different inhibitory drugs into the RVLM in conscious and anesthetized rats

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