Cardiorespiratory and metabolic responses to injection of bicuculline intothe hypothalamic paraventricular nucleus (PVN) of conscious rats

Stimulation of the PVN increases mean arterial pressure (MAP) and heart rat e (HR). However, little is known about its role in modulating ventilation. We tested the hypothesis that the stimulation of the PVN by microinjection of bicuculline methiodide (BMI), a gamma -aminobutyric acid (GABA), recepto r antagonist, increases ventilation in conscious rats. Oxygen consumption w as also evaluated to determine if the ventilatory responses were associated with increases in metabolic rate. Male Sprague-Dawley rats were instrument ed with femoral catheters to measure MAP and HR and cannulae were implanted 1 mm above the PVN. After 5 to 7 days of recovery, metabolic. ventilatory, and cardiovascular responses to artificial cerebrospinal fluid (aCSF) and BMI were evaluated. Rats were given a 50 nl unilateral microinjection of aC SF (the vehicle control) followed by 50 nl of BMI (1 mM) into the other sid e. Microinjection of BMI significantly increased MAP compared to aCSF (145 +/-4 vs. 124 +/-5 mmHg, P<0.02), HR to 460<plus/minus>17 from 362 +/- 22 br eaths/min (P<0.01). Ventilation increased by 300% (P=0.01) by stimulating f requency of breathing (176<plus/minus>14 compared to 79 +/- 12 breaths/min, P<0.005) and increasing tidal volume. Concomitantly, O-2 consumption doubl ed (P<0.006). These data suggest that in the PVN GABA receptors may be impo rtant regulators of cardiopulmonary and metabolic function in conscious rat s. (C) 2001 Published by Elsevier Science B.V.