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Biomedical subjects

D G Harrison

Publications and source records attributed to D G Harrison.

At least 181 records · Page 10Linked to original sources
PubMed1968

The calcium content of human erythrocytes.

1. The calcium content of human erythrocytes, after removal of the buffy coat and washing free from plasma with isotonic sodium chloride, has been determined by atomic absorption spectrophotometry. The mean value found for normal subjects was 0.634 mug/ml. of packed erythrocytes (0.0158 mug-atom/ml.). The corresponding values for magnesium and zinc were 79.7 and 20.1 mug/ml., respectively.2. The calcium is considered to be mostly and perhaps exclusively located in the erythrocyte membrane, since, after osmotic haemolysis, the same amount was found in the ghost cells as was present in the erythrocytes from which they were prepared. By contrast, magnesium and zinc, which are essentially intracellular, were lost to the extent of about 96 and 92%, respectively.3. About 90% of the calcium was removed from erythrocytes by washing with isotonic sodium chloride containing 5 mM ethylenediaminetetraacetate (EDTA), or other complexing agents of high stability constant for calcium. A small fraction of the magnesium but none of the zinc was removed by this treatment.4. Other complexing agents of lower stability constant removed somewhat less calcium from the erythrocytes. Citrate was totally ineffective.5. The buffy coat had a high calcium content, but this could not be removed by washing with EDTA.6. Calcium was also determined in trichloroacetic acid extracts of ghost cells after ashing and treatment with bis-(o-hydroxyphenylimino)-ethane and measuring the red complex spectrophotometrically. The values obtained confirmed the atomic absorption measurements.

Calcium↗
PubMedDate not supplied

Evidence for a role of oxygen-derived free radicals and protein kinase C in nitrate tolerance.

The anti-ischemic effects of organic nitrates are rapidly attenuated due to the development of nitrate tolerance. The mechanisms underlying this phenomenon likely involve several independent factors. As a vasodilator, nitroglycerin activates compensatory neurohumoral mechanisms such as the renin-angiotensin system and increases catecholamine and vasopressin levels, all of which may attenuate its vasodilator potency. Tolerance may be also due to the inability of the vessel to dilate after prolonged treatment with the nitrate. More recent experimental studies have challenged traditional tolerance concepts by demonstrating that tolerance is not associated with sulfhydryl group depletion, reduced nitroglycerin biotransformation, or desensitization of the target enzyme guanylyl-cyclase. Experimental and clinical observations suggest that tolerance may be the consequence of intrinsic abnormalities of the vasculature, including enhanced endothelial production of oxygen-derived free radicals secondary to an activation of NAD(P)H-dependent oxidases and an activation of PKC. Superoxide degrades nitric oxide derived from nitroglycerin (NTG) while C activation causes enhanced sensitivity of the vasculature to circulating neurohormones such as catecholamines, angiotensin II, and serotonin, all of which may compromise the vasodilator potency of NTG. Interestingly, these vascular consequences of in vivo NTG treatment such as superoxide production and PKC activation can be mimicked in vitro by incubating cultured endothelial and smooth muscle cells with angiotensin II. Furthermore, nitrate tolerance and rebound following sudden cessation of prolonged NTG therapy can be prevented by concomitant treatment with high-dose angiotensin-converting enzyme inhibition, angiotensin type 1 receptor blockade, or antioxidants such as hydralazine. Thus one can conclude that neurohumoral counterregulatory mechanisms such as increased circulating levels of angiotensin II may be at least in part responsible for tolerance mechanisms at the cellular level.

Animals↗
PubMedDate not supplied

Reactive oxygen species and the control of vasomotor tone.

During the past 15 years it has become clear that nitric oxide (NO(*)) released by endothelial cells plays a crucial role in vascular homeostasis. In addition to its role as a vasodilator, NO(*) inhibits platelet aggregation and smooth muscle proliferation and decreases the expression of proinflammatory molecules by the endothelium. Importantly, the activity of the NO system is reduced in a variety of pathophysiologic condition, including atherosclerosis, hypercholesterolemia, hypertension, diabetes, cigarette smoking, and aging. The mechanisms whereby these various conditions alter endothelium-dependent vascular relaxation are likely multifactorial. Several lines of evidence have suggested that oxidative inactivation of nitric oxide is likely important in some of these conditions. These studies have shown that in the vessel, a tenuous balance exists between the steady state levels of nitric oxide and the superoxide anion (O2(-*)). In this review, the factors that seem to modulate vascular levels of superoxide anion and nitric oxide will be discussed and evidence that imbalances between these two can predispose to alterations of vascular regulation will be presented.

Animals↗