Key result
Clonidine demonstrates ~9% lower relative vasoconstrictor potency in vivo compared to in vitro.
Why the study?
Differences between in vivo and in vitro alpha-adrenoceptor-mediated contractile effects on human saphenous veins were not well characterized.
What are the comparative contractile effects of noradrenaline, phenylephrine, and clonidine on human saphenous veins in vivo versus in vitro?
What are the comparative contractile effects of noradrenaline, phenylephrine, and clonidine on human saphenous veins in vivo versus in vitro?
p-value: p=<0.05
There are significant differences in the relative potency of alpha-2 adrenoceptor agonists on human saphenous veins when measured in vivo versus in vitro, highlighting the importance of comparative studies.
Alpha-agonists elicit dose-dependent saphenous vein contraction; hypothesis-generating for graft pharmacology, prospective studies needed.
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.
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SJÖUBERG et al. (1989) studied Healthy subjects (n=6). Noradrenaline, phenylephrine, and clonidine vs. In vitro vs in vivo was evaluated on Relative potencies of phenylephrine and clonidine in relation to noradrenaline (p=<0.05). The relative potency of clonidine compared to noradrenaline was significantly lower in vivo (90%) than in vitro (99%, P<0.05), whereas phenylephrine potencies did not differ significantly.
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