Comparative effects of the alpha-adrenoceptor agonists noradrenaline, phenylephrine and clonidine in the human saphenous vein in vivo and in vitro.

The alpha-adrenoceptor-mediated contractile effects of noradrenaline (alpha 1 + alpha 2), phenylephrine (alpha 1) and clonidine (alpha 2) on human saphenous veins were investigated in vivo and in vitro. By infusion (0.3 ml min-1) of the drugs (increasing concentrations in the infused solution) into distended (40 mmHg) saphenous veins in six healthy subjects, local vasoconstriction was induced, measured by a photo-electric device. The drugs induced dose-dependent contractions in all subjects, and dose-response curves were constructed. These were compared with concentration-response curves based on in-vitro results. Macroscopically normal saphenous veins, taken at saphenousectomies, were used, and the preparations were contracted isometrically in organ baths by the agonists. From the curves obtained in vivo and in vitro, the relative potencies of phenylephrine and clonidine (in relation to noradrenaline) were calculated and compared. The relative potencies of phenylephrine in vivo (76%) and in vitro (82%) did not differ significantly. However, the relative potency of clonidine was significantly (P less than 0.05) lower in vivo (90%) than in vitro (99%). Thus, it is concluded that there are differences between the results obtained in vivo and in vitro, stressing the importance of comparative in vivo-in vitro studies.