Abstract-We report that a genetic polymorphism of the ␣ 2 -adrenergic receptor (A2AR) encoded by chromosome 10 is associated with hypertension and an increase in epinephrine-mediated platelet aggregation in humans. The mechanism responsible for this heritable contrast in sensitivity to epinephrine is unknown. We tested our hypothesis that epinephrine-induced platelet aggregation is mediated by activation of chloride transport. We measured epinephrinemediated increases in optical density of gel-filtered platelets suspended in a bicarbonate-buffered physiological salt solution.Compared with platelets incubated in the control buffer (130 mmol/L NaCl), platelets incubated with either bumetanide, a Na/K/2Cl cotransport inhibitor; anthracene-9-carboxylic acid, a chloride channel blocker; or acetazolamide, an agent that blocks ATP-dependent chloride transport had significantly decreased aggregation responses to epinephrine. When measured fluorometrically, epinephrine significantly increased intraplatelet chloride concentrations. Chloride-dependent modifications of epinephrine-induced platelet aggregation were not attributable to changes in A2AR ligand binding characteristics or to the concentration of platelet cAMP. Finally, subthreshold concentrations of epinephrine also potentiated thrombin-induced platelet aggregation, and blockade of chloride transport diminished this synergistic action of epinephrine on thrombin-stimulated platelet aggregation. Heritable differences in epinephrine-mediated platelet aggregation may be attributable to genetic differences in chloride transport in platelets. Furthermore, because we observed a necessary role for chloride transport in epinephrine-mediated platelet aggregation, pharmacological agents that block chloride transport, such as diuretics, may provide salutary protection against vascular thrombosis in patients with hypertension independent of the effect of these drugs on blood pressure. (Hypertension. 1998;31:603-607.)Key Words: adrenergic receptor Ⅲ diuretics Ⅲ thrombosis Ⅲ chloride Ⅲ humans Ⅲ polymorphism Ⅲ blacks Ⅲ genetics T he mechanism by which epinephrine induces platelet aggregation is unknown. In some tissues, such as the respiratory epithelium, activation of the A2AR increases transcellular sodium and chloride cotransport. 1 We reasoned that epinephrine-induced platelet aggregation could also be mediated by A2AR-dependent sodium and chloride cotransport. Accordingly, we tested our hypothesis by measuring epinephrine-mediated platelet aggregation under experimental conditions that would inhibit A2AR-mediated sodium chloride transport, and we measured epinephrine-mediated changes in intracellular chloride concentrations fluorometrically in platelets. Because platelet aggregation may also be dependent on A2AR-mediated changes in the accumulation of intracellular cAMP, we determined the effect of chloride transport inhibition on postreceptor signal transduction by cAMP. Methods Subject RecruitmentWe recruited healthy, fasting, male and female college-age subjects who were...
A successive asymmetric colour-matching task was used to study the changes in colour appearance of simulated Munsell samples. Colour shifts were induced with two Planckian illuminants, standard illuminant A (u'=0.256, v'=0.524) and illuminant S (u'=0.174, v'=0.392). Measurements were conducted with a 20 degrees field and a 120 degrees field. Adaptation period varied from 1 to 30s with the smaller field and from 1 to 60s with the larger field. Colour shifts were specified in terms of a modified Brunswik ratio (BR). Higher values of BR were associated with longer adaptation periods but only when the larger background was used. Supplementary experiments showed that the changes in colour appearance were related to a slight shift in the perceived colour of the background. The timing of the colour shifts are modelled in terms of cone opponent responses. High values of BR correspond to almost complete von Kries adaptation in all three cone types.
We apply an optimization scheme based on rendering of all colors of the enhanced Munsell palette to phosphor-conversion (PC) light-emitting diodes (LEDs). This approach yields combinations of peak wavelengths and bandwidths for white PC LEDs with partial and complete conversion that enable lighting with better quality than that obtained using designs based on the standard color-rendering assessment procedure.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.