STEREOSELECTIVE VASCULAR EFFECTS OF THE (R)-ENANTIOMERS AND (S)-ENANTIOMERS OF PROPRANOLOL AND ATENOLOL

All beta-adrenergic antagonists have an asymmetric carbon atom, and mo st commercially available beta-blockers consist of (R)- and (S)-enanti omers in a fixed 1:1-ratio. The drugs are believed to be contraindicat ed when peripheral vascular disease exists, presumably due to unoppose d alpha-adrenergic vasoconstriction. However, little is known about di rect vascular effects of beta-blockers or of stereoselective effects o n peripheral arteries. Therefore, we investigated the effects on forea rm blood flow (FBF) of brachial artery infusions of the (R)- and (S)en antiomers of propranolol and atenolol (2, 10, and 50 mu g/min each) an d their inhibitory effects on isoprenaline (Iso)-induced vasodilatatio n by forearm venous occlusion plethysmography in 12 healthy subjects. Only (R)propranolol caused an increase in FBF(+21%, p < 0.05), whereas (S)-propranolol and (R)- and (S)-atenolol had no direct effect on per ipheral arteries. Vasodilatation induced by Iso was abolished by (S)-p ropranolol and reduced by (R)-propranolol (-56%, p < 0.05) and (S)aten olol (-68%, p < 0.05), whereas (R)-atenolol had no effect. Our results indicate that the optically pure (R)- and (S)-enantiomers of proprano lol and atenolol do not exert direct vasoconstrictive effects. Further more, our results confirm that predominantly (S)-enantiomers have beta -adrenoceptor blocking effects, but they also show that neither the no n-beta-blocking (R)-enantiomer of propranolol nor the (S)-enantiomer o f the beta(1)-selective agent atenolol is completely devoid of blockin g effects on vascular beta(2)-adrenoceptors.