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Summary:To clarify the effect of extracellular magne sium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2 + concentration on the contractile and endothe lium-dependent dilatory responses were investigated in vitro. The contractions, induced by 1O-8_IO-s M norepi nephrine, were significantly potentiated at low Mg2 + (0,8 mM v. the normal, 1.2 mM). High (1.6 and 2.0 mM) Mg2 + exhibited an inhibitory effect on the contractile re sponses, No significant changes, however, in the EC so values for norepinephrine were found. The endothelium dependent relaxations induced by 1O-8_10-s M acetyl choline were inhibited by high (1.6 and 2.0 mM) Mg2+. Lowering of the Mg2+ concentration to 0.8 mM or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilDuring the past decade, a considerable amount of data has been generated concerning the effect of extracellular magnesium ions (Mg2 + ) on vascular smooth muscle tone and reactivity. Acute with drawal of Mg2 + elevates the basal tone of the arter ies, and contractile responses to various agonists are enhanced in Mg2+ -deficient solutions. Eleva tion of Mg2+ , however, relaxes the smooth muscle and attenuates vasoconstriction (see Altura and Al tura, 1981,1984,1985. Abbreviations used: ECso, 50% effective concentration; EDRF, endothelium-derived relaxing factor. From the original observations of Furchgott and ------------ 161atory responses also shifted the ECso values for acetyl choline to the right. The present results show that the contractile responses of the cerebral arteries are ex tremely susceptible to the changes of Mg2 + concentra tions. In response to contractile and endothelium dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endo thelial receptor. Since Mg2 + deficiency might facilitate the contractile but not the endothelium-dependent relax ant responses, the present study supports a role for Mg2 + deficiency in the development of the cerebral vasospasm.

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SUMMARY The effect of the ganglioside GM1 on the recovery of local cerebral glucose metabolism QCMRgl), recovery kinetics of cerebrocortical electrical activity, cerebral blood flow and redox state as well as histological changes following focal ischemia has been studied in the cat. Ischemia was produced by occlusion of the left middle cerebral artery (MCA), and GM1 (30 mg/kg) was injected intravenously at 30 min after the MCA occluson or at the time of release of the occlusion, at 120 min. Another group of animals were subjected to the same ischemic insult, but without GM1 treatment, and sham-operated treated and not treated cats were also studied. The animals of both GM1-treated and non-treated stroke groups were classified into 2 groups (severe and moderate) depending on the depression of electrocortical activity in the ischemic hemisphere at 30 min of the ischemia. There was a significant increase in local cerebral blood flow in the ischemic area in the treated animals. Additionally there was a significant treatment effect on the left peripheral MCA territory for ICMRgl in the 30 min treated moderate group, (p < .05). This group of animals showed decreased ICMRgl accompanied by less severe histological damage suggesting that GM1 may produce metabolic depression so as to maintain a normal flow-metabolism couple and prevent ischemic structural damage. The possible mechanism of metabolic depression induced by GM1 is briefly discussed.

The effects of stepwise arterial hypotension (MABP: 80, 60, 40 mm Hg) and moderate arterial hypo- and hypertension (MABP: 80, 150-160 mm Hg) on cerebrocortical vascular volume and NAD/NADH redox state were studied in anaesthetized cats. The vascular volume and NADH fluorescence measurements were performed on closed skull preparations using a microscope fluororeflectometer. To determine the possible role of adrenergic alpha-receptors in the autoregulatory adjustment of cerebrocortical vascular volume, some of the animals were pretreated with intra-arterially infused phenoxybenzamine (1 mg/kg). It was found that longlasting stepwise arterial hypotension leads to a gradual increase in cerebrocortical vascular volume and NADH fluorescence. Though the cerebrocortical arteries dilatated considerably at 80 mm Hg, sustained for 30 min, the NAD/NADH redox state failed to be reoxidized but was shifted to a more reduced state. This finding suggests that some factor other than tissue hypoxia is responsible for the dilatation of cerebrocortical vessels during moderate arterial hypotension. When the arterial blood pressure was restored following stepwise arterial hypotension, the cerebrocortical vascular volume did not decrease and the NAD/NADH redox state remained reduced, showing that the autoregulatory capability of the vessels was lost and the tissue metabolism was irreversibly altered. During a 5-min duration of moderate arterial hypo- and hypertension, biphasic changes were obtained in cerebrocortical vascular volume while the NAD/NADH redox state was shifted to a more reduced and oxidized state. Since the dilatation and the constriction of the cerebrocortical vessels during arterial hypo- and hypertension lagged by 40-80 s behind the redox state alterations, it is suggested that the myogenic mechanism has a minor role in CBF autoregulation. Phenoxybenzamine (PBZ) dilatated the cerebrocortical vessels, indicating the existence of an active alpha-receptor-mediated vasoconstrictory tone. Since the extent of autoregulatory vascular volume changes was not affected by PBZ pretreatment, the involvement of adrenergic alpha-receptors in the autoregulation of CBF can be excluded, at least for cats.

Fluorescence of NADH and vascular volume of the brain cortex of chloralose-anesthetized cats were measured by surface fluororeflectometry. A cranial window and superfusion technique was elaborated for the topical inhibition of mitochondrial electron transport in the brain cortex by amytal (inhibits at site I) and cyanide (inhibits at site III). The changes in NAD/NADH redox state and CVV evoked by these electron transport inhibitors were compared with those elicited by anoxic anoxia. Amytal (10(-3)-10(-1) M) and cyanide (10(-5)-10(-2) M) resulted in a concentration-dependent and reversible increase in cortical NAD reduction and vascular volume, but the cerebrocortical vessels were almost completely dilatated long before maximum NAD reduction was reached. Cyanide at 10(-2) M increased cortical NAD reduction and vascular volume as much as anoxic anoxia. Amytal at 10(-1) M induced approximately half of the NAD reduction evoked by 10(-2) M cyanide or anoxic anoxia, but resulted in only slightly less vasodilatation than that following cyanide and anoxic anoxia. Since amytal inhibits mitochondrial electron transport at site I--and cyanide and anoxia at site III--but induces a comparable degree of vasodilatation, it is concluded that cytochrome oxidase cannot be the single molecular oxygen sensor in the brain cortex.

The purpose of this study was to investigate the role of calcium ions in cerebrocortical vasodilatation and oxidized and reduced nicotinamide adenine dinucle otide (NAD/NADH) redox responses evoked by adenosine, anoxia, and epileptic seizures, The brain cor tex of chloralose-anaesthetized cats was treated locally with gallopamil-hydrochloride (D-600) and verapamil (Isoptin®). These organic calcium antagonists decrease the inward movement of calcium ions into vascular smooth muscle cells. Cerebrocortical vascular volume (CVV) and NADH fluorescence were measured in vivo by fluororeflectometry. Adenosine and calcium antagonists were dissolved in artificial cerebrospinal fluid (mock CSF) and applied topically to the brain cortex by superfu sion. Adenosine (10-8 to 10-3 M) resulted in con centration-dependent increases in CVV. The NADI NADH redox state was not altered below adenosine con centrations of 10" M. However, in the concentration range of 10-" to 10-3 M, significant NAD reduction was obtained. Both calcium antagonists increased CVV markedly, but did not bring about significant changes in NAD/NADH ratio and local electrical activity of the ex posed brain cortex. D-600 (2 x 106M) increased CVV as much as did 10-4 M adenosine, but it failed to diminish the vascular and metabolic effects of the adenosine. D-600 (2 x 10-4 M) resulted in an increase in CVV approximately 2.5 times greater than that caused by 10-4 M adenosine In the contraction-relaxation process in vascular smooth muscle-as a common final pathway cytoplasmic free calcium ions play a key role (Bol ton, 1979; Johansson, 1981). Decrease in calcium influx, achieved by organic calcium antagonists

Summary:We investigated the effects of topically ad ministered catecholamines and acetylcholine (ACh) on the cerebrocortical microcirculation and NAD/NADH redox state in chloralose-anesthetized cats. NADH fluo rescence of the brain cortex and the volume of small in tracortical vessels were measured by fluororeflectometry, and in most of the experiments the pial vessels were photographed simultaneously through a cranial window. Cerebrocortical vascular volume (CVV) and the diameter of the pial vessels were decreased, and NADH was oxidized by concentrations of epinephrine and norepi nephrine as low as 3 x 10-8 M. Pial veins constricted approximately twice as much as pial arteries. ACh dila tated pial arteries, slightly constricted pial veins, and in creased CVV, but had no effect on the NAD/NADH redox state. Since pial and intracortical vessels were conThe dual sympathetic and parasympathetic in nervation of cerebral vessels is well recognized, and it has also been proved that cerebral vessels contain both adrenergic and cholinergic receptors (Ku schinsky and Wahl, 1975;Edvinsson and Owman, 1977; Auer et aI., 1981; Harik et ai., 1981; Ulrich et aI., 1982). In spite of this, the role of the autonomic nervous system and its humoral mediators in the regulation of cere bro vascular volume (CVV) and cerebral blood flow (CBF) is still a matter of controversy (Kuschinsky and Wahl, 1975;Kontos,