Summary
Antibiotics which inhibit mammalian protein synthesis at different levels were administered intravenously to anesthetized, adrenergic α-receptor blocked rats. 60 sec after cycloheximide application (2.5, 5, 12.5 and 25 μg/100 g body wt), mean arterial pressure increased an average of 4, 19, 25 and 31% respectively. Mean arterial pressure returned to control values after time lapses varying between 5 and 30 min when maximally effective doses were applied. Neither pressure amplitude nor heart rate were significantly altered. Since blood flow measured in a shunt implanted in the lower aorta also did not change, the pressure response to cyclo-heximide is ascribed to an increase in peripheral vascular resistance.
The pressor response to cycloheximide could be related to blockade of protein synthesis as puromycin (2.5 mg/100 g body wt), another inhibitor of translation, induced a similar increase of arterial pressure. Actinomycin D (30 μg/100 g body wt) which interferes with RNA synthesis had no acute effect on arterial pressure. Furthermore, the acute effect of cycloheximide is reduced after pretreatment with either actinomycin D, puromycin or cycloheximide.
Magnesium deprivation potentiates arterial pressure elevation by cycloheximide and dexamethasone depresses this potentiation. It is postulated that inhibition of protein synthesis at the translation level increases the uptake of contraction triggering calcium by vascular smooth muscle.
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Part of this work appears in abstract form in Proc. Fifth International Congress of Nephrology, 1972.
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Behn, C., Brecht, J.P., Lübbemeier, A. et al. Arterial pressure elevation in response to inhibitors of protein synthesis. Pflugers Arch. 339, 85–95 (1973). https://doi.org/10.1007/BF00587176
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DOI: https://doi.org/10.1007/BF00587176