Influence of the blood pressure level and the mode of contraction on the strength of drug-induced vasoconstriction.

Abstract

1. Under constant pressure or constant flow conditions noradrenaline (NA) was infused into the superior mesenteric artery of the cat in such a manner that there always resulted a local concentration of 2·10−7 g NA/ml. In the case of constant pressure perfusion an electrical coupling was necessary between the perfusing roller pump and the continuously adjustable infusion pump. 2. For the condition of constant pressure perfusion the constrictor response caused by NA is expressed by the resulting flow reduction ΔI. With rising pressure levels this value increases at first in a steep manner, then it reaches a flat maximum. If the reduction of flow is related to the initial flow by the expression ΔI/I, the appearance of a maximum is still more obvious. 3. Under constant flow perfusion the NA-induced pressure increase ΔP first rises with rising initial pressure and also shows a clear maximum. Only after this maximum the often described negative regression lines related to the resting intraluminal pressure are approximately valid. The existence of an optimum in the physiological pressure range strongly limits the “law of initial value” of Wilder, but is in good agreement with results obtained on the isolated vascular smooth muscle. 4. A comparison of the constrictor responses during constant pressure or constant flow perfusion is made by the increase of the respective resistances. Thus larger values result under constant pressure perfusion at initial pressures above 80 mm Hg. Below this pressure level the constant flow perfusion leads to larger values with a maximum at 60 mm Hg. The cause of the different optima for both perfusion modes is discussed. 5. The evidence for the appearance of an optimum for vasoconstrictions as dependent on the intraluminal pressure can be offered only if the experiments are extended over a very wide range of pressures. Thus the discrepancy with former investigations is interpreted. Now an optimum of constrictions could be found under both constant pressure and constant flow perfusion, the former equalling more isotonic conditions, the latter more isometric conditions.