Differential pharmacologic sensitivities of phosphodiesterase-3 inhibitors among human isolated gastroepiploic, internal mammary, and radial arteries.

UNLABELLED: Systematic investigations of the actions of phosphodiesterase (PDE)-3 inhibitors on different human vascular tissues have not been performed. We investigated the effects of specific PDE-3 inhibitors (olprinone, milrinone, and amrinone) on contracted human gastroepiploic arteries (n = 70), internal mammary arteries (n = 72), and radial arteries (n = 70) harvested from a total of 134 patients, all of whom were undergoing coronary artery bypass surgery. Each of these PDE-3 inhibitors dose-dependently diminished the contractile responses to 10(-6) mol/L norepinephrine and to either 10(-9) or 10(-8) mol/L of the thromboxane A2 analog U46619. In inducing vasorelaxations, these inhibitors were significantly more potent in norepinephrine-contracted rings than in those contracted with U46619. Further, at concentrations similar to the maximum therapeutic plasma concentrations (10(-7) mol/L olprinone; 10(-6) mol/L milrinone; 10(-5) mol/L amrinone) olprinone and milrinone were more potent at inducing relaxations than amrinone in gastroepiploic arteries and radial arteries, whereas in internal mammary arteries milrinone was more potent than the others. These results suggest different activities for the three PDE-3 inhibitors among human arteries located in different regions and may be informative about the effectiveness of these inhibitors in preventing spasms in the various arterial grafts used in revascularization. IMPLICATIONS: Because three phosphodiesterase-3 inhibitors (milrinone, olprinone, and amrinone) differed in their vasodilator potencies (against the contractile response to either norepinephrine or a thromboxane A2 analog) among human arteries removed from different parts of the body, their vascular relaxation profiles should be considered before they are used clinically.

The variable effects of dopamine among human isolated arteries commonly used for coronary bypass grafts.

UNLABELLED: The direct actions of dopamine on human arterial coronary bypass grafts are not well known. We investigated its effects on isolated rings cut from radial arteries (RA), gastroepiploic arteries (GEA), and internal mammary arteries (IMA) harvested from patients undergoing coronary artery bypass surgery. Dopamine produced dose-dependent contractile responses in RA, an effect independent of the presence of a functional endothelium. The contractions were enhanced by the dopamine A(1) (DA(1))-receptor antagonist SCH23390, whereas they were blocked by an alpha(1)-adrenergic antagonist, prazosin. Results qualitatively similar to these were obtained in both GEA and IMA, although the contractile responses were far smaller. In RA, DA enhanced the norepinephrine (NE)-induced contraction, and this action of dopamine was enhanced by SCH23390. In GEA, small concentrations (<10(-7) mol/L) of DA attenuated the NE-induced contraction but larger concentrations did not. In IMA, DA induced a vasorelaxation on the NE-contraction only at higher concentrations (10(-6)-10(-5) mol/L). In both GEA and IMA, the dopamine-induced vasorelaxations on the NE contraction were completely inhibited by SCH23390. These results suggest that the affinities of DA for DA(1)- and alpha(1)-adrenergic receptors may explain its variable contractile and vasorelaxant effects among these arteries. IMPLICATIONS: Differing affinities of dopamine for dopamine A(1)- and alpha(1)-adrenergic receptors may lead to it having variable contractile and vasorelaxant effects among the arteries supplying grafts for coronary bypass surgery.