Cardiorespiratory and metabolic responses to injection of bicuculline into the hypothalamic paraventricular nucleus (PVN) of conscious rats.
Stimulation of the PVN increases mean arterial pressure (MAP) and heart rate (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)(A) receptor antagonist, increases ventilation in conscious rats. Oxygen consumption was also evaluated to determine if the ventilatory responses were associated with increases in metabolic rate. Male Sprague--Dawley rats were instrumented 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 aCSF (the vehicle control) followed by 50 n1 of BMI (1 mM) into the other side. Microinjection of BMI significantly increased MAP compared to aCSF (145+/-4 vs. 124+/-5 mmHg, P<0.02), HR to 460+/-17 from 362+/-22 breaths/min (P<0.01). Ventilation increased by 300% (P=0.01) by stimulating frequency of breathing (176+/-14 compared to 79+/-12 breaths/min, P<0.005) and increasing tidal volume. Concomitantly, O(2) consumption doubled (P<0.006). These data suggest that in the PVN GABA receptors may be important regulators of cardiopulmonary and metabolic function in conscious rats.
Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, 414 East Clark Street, Vermillion, SD 57069, USA. eschlenk@usd.edu
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Schlenker
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Barnes
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Hansen
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Martin
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003243:Consciousness / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline