Platelet and brain α₂‐adrenoceptors and cardiovascular sensitivity to agonists in dogs suffering from endotoxic shock

Abstract

We examined the changes in alpha 2-adrenoceptor binding on platelet and brain membranes of dogs treated with a non-lethal dose of endotoxin (0.1 mg/kg intravenously), and the alpha 2-adrenoceptor mediated cardiovascular effects during endotoxin shock. At 2 h, 24 h, and 7 days after endotoxin administration, the number of binding sites (Bmax) of [3H]yohimbine binding decreased and equilibrium dissociation constants (Kd) increased in platelets, whereas both Bmax and Kd decreased in either cerebral cortex or medulla oblongata. After 30 days of endotoxin administration, there were no significant differences in Bmax or Kd between the treated and untreated animals in both platelets and brain tissues. Significant positive correlations were observed for Bmax values between platelets and brain tissues, although negative correlations for Kd values between platelets and brain were not significant. Significant negative correlations were also observed between plasma catecholamine concentrations and platelet alpha 2-adrenoceptor number, and between plasma noradrenaline and medulla alpha 2-adrenoceptor number. Pretreatment with E coli endotoxin diminished cardiovascular effects such as bradycardia, hypotension, and increase in systemic vascular resistance induced by either i.v. clonidine or xylazine. This suggests that alpha 2-adrenoceptor activity is impaired in the central nervous system as well as in the peripheral vascular system during endotoxin shock. Therefore, platelets may in part represent a good model which reflects the alpha 2-adrenoceptor changes in the central nervous system and peripheral vascular system during and after endotoxin shock.

Adrenoceptor Hyporeactivity Is Responsible for Escherichia coli Endotoxin–Induced Acute Vascular Dysfunction in Humans

“…29 Internalization of vascular ␣-adrenoceptors could also contribute to the hypodynamic states, as shown in rat hearts 30 or platelets. 31 Another explanation for our finding of decreased responses to catecholamines after LPS could be that catecholamines are inactivated by free radicals, including superoxide anions (O 2 Ϫ ). The production of O 2 Ϫ is increased in sepsis as in other inflammatory conditions and could play a role in the pathogenesis of hemodynamic instability and organ dysfunction during septic shock.…”

Late Referral to a Nephrologist Increases the Risk of Uremia-Related Cardiac Hypertrophy in Patients on Hemodialysis

“…It is well known that various markers of malnutrition and inflammation are strong independent predictors of LVH and mortality in dialysis patients [13, 24, 25]. Therefore, the impact of ‘uremia-related’ risk factors, such as inflammation and malnutrition and secondary hyperparathyroidism, on cardiovascular mortality may be so strong in dialysis patients that they can obscure the impact of common ‘traditional’ risk factors, such as hypertension, tobacco smoking and dyslipidemia [26].…”

Effects of Imidazoline and Non-Imidazoline α-Adrenergic Agents on Rabbit Platelet Aggregation

“…Platelet membrane preparation was carried out by a modification of previous methods [29]. The PRP, which was prepared by the method mentioned above, was centrifuged for 10 min at 2,000 g to obtain a platelet pellet.…”

“…Saturation binding experiments to platelet membranes were carried out according to a slight modification of methods described previously [29]. Radioligand binding assay to platelet non-adrenergic I 1 and I 2 receptors was performed using [ 3 H]-clonidine and [ 3 H]-idazoxan, respectively, which have been reported previously [23,30].…”