THE EFFECTS OF PAPAVERINE ON PHORBOL DIBUTYRATE-INDUCED VASOCONSTRICTION IN BRAIN SLICE MICROVESSELS

Papaverine (PPV) is a nonspecific vasodilator with widespread clinical uses in the treatment of arterial spasm. It has also been utilized in an attempt to reverse cerebral vasospasm. Recent angiographic results have demonstrated significant reversal of vasospasm in large vessels after selective intra-arterial application of PPV; however, these impr essive results lacked good clinical correlation. In this study, phorbo l dibutyrate was used to stimulate protein kinase C in an in vitro mod el of cerebral microvessels. Papaverine was found to elicit a dose-dep endent exacerbation of phorbol dibutyrate-induced microvascular constr iction in this model system. Because protein kinase C is thought to pl ay a key role in the development of cerebral vasospasm, PPV-induced va soconstriction represents a potentially important deleterious effect t hat may not be apparent on angiography. Such a constrictor response ma y compromise the beneficial vasodilatory effect seen with intra-arteri al injection of PPV.