Anomalous responses of tumor vasculature to norepinephrine and prostaglandin E2 in the rabbit.

SUMMARY We used 25-/im microspheres to compare blood flow to the V-2 carcinoma in the awake, unanesthetized rabbit with blood flow to other organs. Injection of norepinephrine (50 jig) into the left ventricle caused a 41fold [95% confidence interval = (25-69)] increase in tumor vascular resistance (P < 0.01). This was more than one order of magnitude greater than the increase in resistance in any other organ. Prostaglandin E2 (50 fig) injected into the left ventricle caused a 7-fold (4-13) increase in tumor vascular resistance (P < 0.01) and no significant increase of the vascular resistance of other organs. The change in tumor vascular resistance was not completely due to an increased level of circulating catecholamines because a 2-fold (1.6-3.4) increase in the resistance (P < 0.01) was seen when prostaglandin E, was injected into the left ventricle of animals pretreated with phenoxybenzamine. The prostaglandin E2-induced tumor vasoconstriction was not due to an increased level of circulating angiotensin II because in animals in which a and angiotensin receptors were blocked, prostaglandin E2 increased the tumor vascular resistance by a factor of 3 (2.3-5.5) (P < 0.01). The tumor vasculature appears to be hypersensitive to a-receptor activation and responds to prostaglandin E2 with vasoconstriction which cannot be accounted for by an increased level of circulating catecholamines or angiotensin II. In these experiments, the vasculature of the tumor responded to pharmacological agents in a manner that was not displayed by the vasculature of other organs. It may be possible to selectively control tumor blood flow without adversely affecting the blood flow to other organs of the host.

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