CYCLIC-NUCLEOTIDES AND CEREBROVASCULAR TONE IN NEWBORN PIGS

Relationships between cyclic nucleotides and cerebrovascular tone were investigated using closed cranial windows in anesthetized newborn pig s. Pial arteriolar diameter was monitored and cerebrospinal fluid (CSF ) was collected from beneath the cranial window. Adenosine 3',5'-cycli c monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) concentrations in CSF were 1,690 +/- 200 and 730 +/- 40 fmol/ml, resp ectively. Topically applied isozyme-selective and nonselective inhibit ors [3-isobutyl-1-methylxanthine (IBMX), theophylline, Ro 201724, dipy ridamole, zaprinast, calmidazolium, and W-7] of cyclic nucleotide phos phodiesterases dilated pial arterioles with concomitant increases in c AMP and/or cGMP levels in CSF. Topical application of dibutyryl-cAMP a nd dibutyryl-cGMP also resulted in pial arteriolar dilation. Ten-minut e hypercapnia, which results in pial arteriolar dilation, increased cA MP to 5,240 +/- 900 and cGMP to 1,350 +/- 200 fmol/ml. IBMX and zaprin ast potentiated the increases in cAMP and cGMP as well as the cerebrov ascular dilation in response to hypercapnia. These data suggest that c yclic nucleotides contribute to regulation of cerebral vascular tone d uring control conditions. Furthermore, cAMP and/or cGMP appears to be involved in arterial vasodilation in response to hypercapnia in newbor n pigs.