Blood pressure changes and sympathetic function in rats given cyclohexylamine by intravenous infusion.
Intravenous infusion of cyclohexylamine (30-120 mg/kg) caused a dose-dependent increase in blood pressure in urethane-anesthetized rats. The increase in blood pressure was inversely related to the duration of the infusion. The blood pressure returned to baseline values (+/- 5 mm Hg) within 60 min of the end of the infusion after doses of 30 and 60 mg/kg were administered over 20 and 40 min. The plasma concentrations of cyclohexylamine were related linearly to the administered dose and decreased only 27% between the end of the infusion and 60 min later. The concentration-effect relationship showed clockwise hysteresis, indicative of tachyphylaxis, as has been reported in humans (Eichelbaum et al., 1974). Administration of bolus doses of tyramine at the end of the infusion or 60 min later demonstrated the presence of an indirect sympathomimetic response, although this was attenuated to a greater extent by high doses and more rapid infusions of cyclohexylamine. An almost complete loss of response to tyramine was found only in animals given 120 mg/kg over 40 min. The presence of a tyramine response 60 min after the infusion of 60 mg/kg occurred when there was an essentially complete reversal of the hypertensive effect of cyclohexylamine. These data indicate that the hypertensive effect of the indirectly acting sympathomimetic amine cyclohexylamine occurs primarily during rapid increases in plasma concentrations. Tachyphylaxis develops rapidly after the cessation of the infusion which is probably due largely to reuptake of released noradrenaline at low doses and depletion of releasable noradrenaline at high doses.
Buss
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Clinical Pharmacology Group, University of Southampton, Bassett Crescent East, United Kingdom.
Renwick
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003514:Cyclohexylamines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013618:Tachyphylaxis; D014439:Tyramine / Q000494:pharmacology
D003514:Cyclohexylamines; D014439:Tyramine