Effect of the Organic Calcium Antagonist D-600 on Cerebrocortical Vascular and Redox Responses Evoked by Adenosine, Anoxia, and Epilepsy

Abstract

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

Effect of Topically Administered Epinephrine, Norepinephrine, and Acetylcholine on Cerebrocortical Circulation and the NAD/NADH Redox State

“…In our experiments, although ACh dilatated pial arteries and increased CVV, NADH oxidation was not altered significantly. Similar results were ob tained in another study with organic calcium an tagonists (Kovach et al, 1983), which are more potent vasodilatators than ACh. Since under these circumstances CPP remains constant, it can be pre sumed that CBF and cerebrocortical oxygen supply are elevated (Meier and Zierler, 1954).…”

Contribution of Flow-Dependent Vasomotor Mechanisms to the Autoregulation of Cerebral Blood Flow

“…This interpretation of “autoregulation” means adjusting CBF to the metabolic demands and to function of neural tissues. Although metabolic regulation of CBF [2, 5, 13, 14, 28] is obviously an important issue, in this review we define autoregulation to be vasomotor responses to changes in hemodynamic forces achieved by mechanisms intrinsic to the vascular wall, rendering the cerebral blood perfusion independent from changes in systemic blood pressure, and without activating metabolic, chemical, glial, neural and other (for example capillary blood flow regulation by pericytes) regulatory mechanisms [1, 2, 5–11, 18, 19, 29]. Because changes in pressure are accompanied by changes in flow, in vivo responses of cerebral vessels to changes in hemodynamics are most likely a combination of pressure and flow-induced mechanisms [30–33].…”

Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies

“…The connection between the concentration of K ϩ and the decrease in mitochondrial NADH was shown in cat hippocampus (192). The effect of seizures on mitochondrial NADH was investigated later on by other groups, mainly in cat models (66,69,100,131,143,220,226,236,253,254). Vern et al (253) showed that epileptic activity, induced in hypotensive cats, caused an increase in NADH instead of a decrease.…”