Effect of phenoxybenzamine, propranolol, phenylephrine and isoproterenol on the circulation of rats bearing Guérin carcinoma.

Effects of phenoxybenzamine (1 mg per 100 g i.v.), propranolol (0.2 mg per 100 g i.v.), phenylephrine (0.1--0.3--1.0--3.0 micrograms per 100 g per min) and isoproterenol (0.01--0.03--0.1--0.3 micrograms per 100 g per min) were studied on cardiac output (Evans-blue dilution), organ and tumour blood flows (Sapirstein's isotope indicator dilution technique) in rats bearing Guérin carcinoma. In agreement with our earlier results data for haematocrit, blood pressure, TPR and organ vascular resistance were lower whereas cardiac index and organ blood flow were higher in control untreated tumour-bearing animals than in untreated normal rats. Phenoxybenzamine, depending on tumour size, decreased blood pressure, TPR and vascular resistance of organs, while it was found ineffective in rats with tumours of very large size (60--80 g). Propranolol treatment produced slight and similar effects in both normal and tumour-bearing rats. Phenylephrine enhanced peripheral resistance as a function of log dose in both normal and tumour bearing animals, nevertheless in the latter group it elicited more marked responses in the vascular bed of the kidneys, intestines and skin. The vasodilatory log dose dependent effect of isoproterenol was not present in tumour-bearing rats. In addition to the anaemia, the continuous decrease of alpha adrenergic activity in the systemic circulation parallel with tumour growth appears to be the most reasonable explanation for the "hyperkinesis" observed in tumour-bearing rats. Resistance of tumour vascular bed was increased by both phenoxybenzamine and propranolol. During the course of phenylephrine infusion (1.0 or 3.0 micrograms per min) the resistance of tumour vessels was more increased than that of other organs. Isoproterenol infusion resulted in a vasoconstriction of the tumour vessel. It appears that with maximally dilated vessels, vasoconstriction remains the only possible vascular response in Guérin carcinoma. In the vascular bed of the tumour a preponderance of beta adrenergic receptors also seems to be feasible.