Cardiovascular responses to nifedipine in anaesthetized rats with abnormal blood gas/pH levels.
1. Blood pressure and pulse rate responses to intravenously (i.v.) administered nifedipine were studied in chloralose-anaesthetized rats subjected to hypoxaemia, hyperoxaemia, alkalosis, acidosis, hypocarbia with alkalosis, or hypercarbia with acidosis. 2. Ventilation with a gas mixture of 17% O2, 28% O2, or 23% O2 with 5% CO2 at a fixed stroke volume (10 mL/kg) and rate (80 strokes/min) induced hypoxaemia, hyperoxaemia or hypercarbia, respectively. Hypocarbia was induced by ventilation with 17% O2 at 160 strokes/min. Acidosis or alkalosis was produced by intravenous infusion of 1 mol/L HCl or 1 mol/L NaHCO3, respectively, in animals ventilated with room air. 3. There were significant decreases in blood pressure and pulse rate during acidosis, and increases in pulse rate during alkalosis and hypercarbia. No marked changes in these parameters were observed under the other experimental conditions. 4. The control animals showed a dose-dependent decrease in blood pressure without marked changes in pulse rate in response to nifedipine injection. 5. Significant reductions in the hypotensive effect of nifedipine were observed in rats subjected to alkalosis, acidosis, or hypercarbia. A similar tendency was also found during hypocarbia while the responses to nifedipine during hypoxaemia and hyperoxaemia were statistically the same as those in the controls. 6. It is concluded that alterations of blood pH reduce the hypotensive effect of nifedipine, and we suggest that blood pH changes probably play a more important role than PO2 or PCO2 abnormalities in altering the cardiovascular responses to nifedipine in hypoventilated or hyperventilated rats.
Achike
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Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Sassoon Road, Hong Kong.
Dai
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D000138:Acidosis / Q000097:blood*; D000471:Alkalosis / Q000097:blood*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood*; D002319:Cardiovascular System / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D011674:Pulse / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D002245:Carbon Dioxide; D009543:Nifedipine; D010100:Oxygen