Secondary Fall in Blood Pressure Following Noradrenaline Infusion in the Cat

Abstract

It is frequently noted that the rise in blood pressure following single injections of noradrenaline in doses above 5-10 pg in the anaesthetized cat is followed by (1) a fall in blood pressure to subnormal levels, and (2) a temporarily diminished sensitivity to subsequent small doses of noradrenaline.It is common experience that the sudden withdrawal of a noradrenaline infusion in man is sometimes followed by a fall in blood pressure below the pre-infusional level, and this may necessitate a prompt recommencement of the infusion, often in a higher dosage than previously given.Although this secondary fall has been observed by severaI investigators there seems to be no generally accepted explanation of this phenomenon. BLACKET, PICKERING and WILSON (1950) have studied the effect of prolonged infusion of noradrenaline in the unanaesthetized rabbit. With doses not exceeding 3 pglkglmin. they found that the blood pressure in most animals had a tendency to fall and that, on termination of the infusion, there was an abrupt and severe drop in blood pressure, lasting for a day or more. The authors discuss various -possible mechanisms for the observed fall in blood pressure and consider a release of vasodilator substances the most likely explanation of the effect. Similar observations have been made earlier with adrenaline (BAINBRIDGE and TREVAN 1917, ERLANGER and GASSER 1919 and others).

Effect of l-norepinephrine on left ventricular diastolic pressures in man

“…It appears that haemodynamic changes occur in the course of such a continuous infusion which may yield conflicting results unless measurements are made at definite time intervals. Dun6r and von Euler (1957) noted a decline in systemic blood pressure during prolonged infusion of l-norepinephrine in cats, and similar observations were reported by Lever, Mowbray, and Peart (1961) and more recently by Weglarz and Killip (1963). The latter observers found in dogs that systemic blood pressure rises maximally in the first four minutes and then begins to fall.…”

l-Norepinephrine and the Pulmonary Circulation

“…Duner and von Euler [18] n o ted a decline in system ic blood pressure during prolonged infusion of 1-norcpinephrine in cats, and sim ilar observations were reported b y Lever et al [19] and m ore recently by 1Veglarz and K illip [20]. These observers found in dogs t h a t system ic blood pressure rises m axim ally in th e first 4 m inutes and th e n began to fall.…”

The Origin of the Decline in the Vasopressor Response to Infused Noradrenaline in the Pithed Rat

“…Respiring rats with 100% oxygen from the beginning of an experiment did not prevent the fall in arterial blood pressure during continuous infusion of noradrenaline. DISCUSSION It has frequently been reported that the continuous infusion of adrenaline or noradrenaline results in a rise of systemic blood pressure which is not maintained despite the continuation of the infusion, and that when the infusion is stopped there is a longlasting fall in pressure below the pre-infusion level (Bainbridge & Trevan, 1917;Erlanger & Gasser, 1919;Freeman, Freedman & Miller, 1941;Blacket, Pickering & Wilson, 1950;Duner & von Euler, 1957). In most instances intact animals were used, so that the infusion caused a rise in pressure above, often far above, normal.…”