Effect of γ-Hydroxybutyrate on the Reactivity of Pial Arteries before and after Ischemia

Abstract

Summary: The effect of "{-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a pe riod of transient ischemia induced by air embolism. The vascular reactions were determined during the perivas cular microapplication of artificial CSFs with in creasing concentrations of adenosine (10-11_ 10-3 M), H + (pH 5.1-7. 6), or K + (0-JO mM). During nonischemic conditions the pial arterial reactivity to adenosine and H+, but not to K +, was significantly increased by GHB (250 mg/kg i. v. ) when compared with the control reac tivity. After cerebral ischemia the reactivity to adenosine was abolished with and without the administration of GHB prior to air embolism. The reactivity to K + was 'Y-Hydroxybutyrate (GHB) is a naturally occur ring cerebral metabolite (Roth and Giarman, 1970;Walters and Roth, 1977) with an unknown physio logical role. Although the conversion of GHB to 'Y aminobutyrate appears to be possible (Vayer et aI., 1985), the relevance of this step is a matter of dis pute. There is also evidence that GHB fulfills the criteria of a neurotransmitter or -modulator (Hasli and Hasli, 1983;Maitre and Mandel, 1984). The ex ogenous administration of GHB induces a depres sion of consciousness that is reflected by charac teristic changes in the EEG resembling a state of nonconvulsant epilepsy (Winters and Spooner, 1965;Snead et at., 1976) . During the action of GHB, the cerebral glucose utilization is markedly reduced in the awake rat (Kuschinsky et aI., 1985). Address correspondence and reprint requests to Prof. Dr. w.Kuschinsky at Physiologisches Institut der Universitat, Nu f3allee II, D-5300 Bonn I, F.R.G.Abbreviation used: GHB, 'Y-hydroxybutyrate. 658partly preserved but not increased by GHB when com pared with previous results without GHB. In contrast GHB improved the postischemic reactivity to perivas cular H+ that had been found to be abolished in previous experiments without GHB. The perivascular microappli cation of GHB showed no influence of GHB on the vas cular diameter. An important finding of the present study is the demonstration of an increase in cerebrovascular re activity, which may give scope for therapeutic improve ment of the regulation of CBF in pathophysiological conditions. Key Words: Cerebral ischemia-,,{-Hydroxy butyrate -Metabolic factors -Microapplication tech nique-Protection-Vasoreactivity.by pharmacological doses of GHB might be ex plained by an altered reactivity of the cerebral vessels to local metabolic factors. If such an effect also exists at physiological concentrations of GHB, a physiological role of GHB could be to modulate the cerebrovascular reactivity to metabolic stimuli.To test the possibilities of a physiological or phar macological action of GHB on the vascular reac tivity, the responsiveness of pial arteries to adeno sine, H +, and K + was determined during the action of GHB. These three substances play a major role in the local regulation of CBF under physiological conditions (Kusc...

Effect of γ-Hydroxybutyrate on Local and Global Glucose Metabolism in the Anesthetized Cat Brain

“…In the present study, no increase in cerebral metabo lism was found. In conjunction with our previous findings of an increased cerebrovascular reactivity under experimental conditions identical with those of the present study (Haller et al, 1986), our data do not support the concept of a direct relationship be tween cerebral metabolism and cerebrovascular re activity.…”

“…For the comparison of the global measurements during the control phase and after GHB, multivariate analysis of variance (MANOV A) with mixed effects was employed as previously described (Haller et al, 1986). The Statis tical Package for the Social Sciences (SPSSX) (Nie et al, 1983) was used for the computations.…”

Effect of Moderate Endothelial Damage on the in vivo Reactivity of Pial Arteries to Norepinephrine and Serotonin

“…The concentration-response curves and the changes in vascular diameter between the two experimental phases (control/after air embolism) were analyzed as previously described [10], using multi variate analysis o f variance (MANOVA) with mixed effects. For the computation the program MANOVA o f the SPSS' package was used [11], A level o f p < 0.05 was accepted as significant in all statistical tests.…”

“…Arterial blood pressure was continuously recorded from a catheter in a femoral artery, and the acid-base status was checked at regular intervals; the adjacent vein was cannulated for the continuous infu sion o f Tyrode's solution. A catheter was advanced into the innom inate artery via the right axillary artery to induce arterial cerebral air embolism as previously described [10]. After the animals had been put into a stereotaxic frame, a right temporoparietal craniotomy was performed, and the cortical surface was visualized under a thick layer of warmed paraffin oil.…”

“…Fifteen arteries from 6 embolized brains were examined by scanning electron microscopy. Two arteries from 1 nonembolized, craniotomized animal were used as control observations in conjunction with the arteries from 4 control animals used in a previous study [10]. Typical scanning electron micrographs are shown in figure 5.…”