CARDIAC AND VASCULAR CHANGES IN ACUTE TOLERANCE TO NOREPINEPHRINE INFUSIONS

¹ Department of Pharmacology, Marquette School of Medicine, Milwaukee, Wisconsin

The decline in arterial pressure which follows the initial rise during i.v. infusion of norepinephrine (acute tolerance) was studied in anesthetized dogs given constant rate continuous infusions for 60 mm (0.156-5.00 µg/kg/min). The most striking part of the decline in arterial pressure took place during the first 15 min of infusion. Blood pressure responses were found to follow the same pattern in open-chest dogs in which continuous measurements were also made of cardiac output and forelimb perfusion pressure. All norepinephrine dosages given produced significant initial increases in arterial pressure, cardiac output and forelimb vascular resistance. At low norepinephrine infusion rates, tolerance was confined to the first 15 min and was associated with a diminishing forelimb vascular resistance and a rising cardiac output. At higher dosages, tolerance was accompanied both by a short-lived decline in forelimb vascular resistance and a nearly parallel longer lasting decrease in cardiac output. These results indicate that tolerance occurs over at least a 30-fold dosage range of norepinephrine, that alteration in vascular resistance is responsible at low dosage and that, at higher dosage, both vascular resistance and cardiac output are involved, the latter being the more important as infusion progresses.

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