A modification of the methods is described which makes it possible to measure pyridine nucleotide fluorescence from the brain cortex in vivo without interference from movement and hemodynamic artifacts. Movement artifacts were eliminated by the use of a window technique. Fluorescence changes due to changes in hemoglobin oxygenation have been eliminated by measuring fluorescence at an isobestic wavelength of the hemoglobin-oxyhemoglobin reaction. The interference due to changes in red blood cell concentration has been studied by simultaneous measurements of fluorescence and ultraviolet reflection. Hemodilution revealed a linear relationship between the fluorescence from the pyridine nucleotide and reflected ultraviolet light. The ratio between the light absorption changes was approximately unity under the particular optical geometry employed in this study. This method has been used to measure fluorescence changes produced by nitrogen anoxia. The technique is discussed in relation to previous methods and the effects of anoxia are compared to previous findings.

1. We studied the effects of NG-nitro-L-arginine (NOLA), a potent inhibitor of the L-arginine-nitric oxide pathway, and L-arginine, the precursor of nitric oxide, on regional cerebral blood flow, electrocortical activity and ex vivo cerebrovascular reactivity in the cat. Flow was measured via radiolabelled microspheres, and vascular responses were studied by measuring isometric tension of isolated middle cerebral arterial rings. 2. NOLA (30 mg kg-1 bolus followed by 1 mg kg-1 min-1 infusion) caused an approximately 40 mmHg elevation in the mean arterial blood pressure, a regionally heterogenous increase of the regional cerebrovascular resistance and a decrease in the regional cerebral blood flow 15 and 40 min after the start of its administration. In contrast L-arginine (30 mg kg-1 bolus followed by 10 mg kg-1 min-1 infusion) did not alter blood pressure, cerebrovascular resistance nor regional cerebral blood flow 15 min after the start of its administration. The NOLA-induced changes in tissue flow were the most pronounced in the cerebellum, pituitary and medulla oblongata, whereas there was no decrease in the flow of the cortex and white matter. 3. NOLA caused characteristic changes in total fronto-occipital EEG power and in power spectra which were unlikely to have been due to cerebral ischaemia. In addition, the ex vivo reactivity of the middle cerebral arteries showed signs of impaired endothelial nitric oxide synthesis: there were enhanced noradrenaline-induced contractions and N-ethoxycarbonyl-3-morpholino-sydnonimine (SIN-1)-induced relaxations and markedly attenuated acetylcholine- and ATP-induced relaxations after NOLA treatment. 4. The present data indicate that resting cerebral blood flow and cerebrovascular resistance are regulated by nitric oxide derived from L-arginine in a regionally heterogenous way and that exogenous L-arginine availability is not a limiting factor in this nitric oxide generation. Possibly, both the vascular endothelium and the neurons contribute to this basal nitric oxide release.

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Electrolyte concentration values in interstitial fluid samples that have been reported by a number of authors were markedly different from those of a hypothetical ultrafiltrate of plasma. Because no adequate explanation has been provided for the discrepancy, we attempted to study the question 1) by measuring ion and protein concentration in the plasma and in the interstitial fluid samples, and 2) by constructing a theoretical model for ion distribution. Subcutaneous interstitial fluid samples were collected in rats by the implanted capsule and by the liquid paraffin cavity techniques. The samples were analyzed for sodium, potassium, calcium, chloride, total protein, and protein fractions. The ion distribution between vascular and interstitial compartments was found to correspond to the Donnan equilibrium. On theoretical ground it was concluded: the Donnan distribution is valid, if the size of "free-fluid spaces" is relatively large (r greater than 0.03 micron) compared with the rather short range of electrostatic interactions (approximately 0.8 nm). Due to the relatively small difference in protein concentrations between blood plasma and interstitial fluid and to the short range of electrostatic interactions, the influence of proteins on the distribution of small ions is negligible.

Many authors have studied the hemodynamics of the dental pulp; however, there are scarcely any data regarding the involvement of the L-arginine/nitric oxide pathway in the regulatory mechanism. Thus, we have examined the physiological effects of (1) NG-nitro-L-arginine as an inhibitor of nitric oxide synthesis and (2) the nitric oxide donor 3-morpholinosydnonimine on blood flow and vascular resistance in the canines of anesthetized cats to study the potential involvement of nitric oxide in the regulation of dental vascular homeostasis. Mean arterial blood pressure, heart rate, blood gases, pH, cardiac output, and tissue blood flow were determined prior to and 15 min after i.v. administration of either NG-nitro-L-arginine (30 mg/kg, n = 9) or 3-morpholinosydnonimine (1 mg/kg, n = 7). Blood flow was measured by radioactive-labeled microspheres. There were no significant differences in baseline parameters between the two groups of cats. The dental pulp blood flow decreased to 53 +/- 13% (p < 0.01) of the control level after NG-nitro-L-arginine administration, while it decreased only slightly (to 82 +/- 12%) after 3-morpholinosydnonimine administration. The dental pulp's vascular resistance increased to 367 +/- 69% (p < 0.01) of the control level after NG-nitro-L-arginine, while it decreased to 73 +/- 10% (p < 0.05) of control after 3-morpholinosydnonimine. We found that the L-arginine/nitric oxide pathway plays an important role in the regulation of pulpal blood circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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In conclusion, the reviewed results clearly suggest that vital functions of the brain -in spite of the well-developed autoregulatory mechanisms-are impaired during long-lasting hypovolemic and other shock conditions. The insufficiency of the cerebrocortical and hypothalamic regulatory mechanisms can contribute to the development of the irreversible shock. In other words, failure of the body suffering from shock to restore the homeostatic equilibrium can be attributed to the inadequacy of the central nervous servocontrol system. According to the available results, the regional cerebral microcirculatory defect develops through sludge formation. The unevenly distributed local brain damage could be the background of the functional impairment. The focal appearance suggest that, in addition to generalized (bloody borne) changes, local factors play an important role in the production of patchy ischemic areas in the brain.

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.