methylatropine and Hyperglycemia

The purpose of this study was to investigate the involvement of acetylcholinesterase (AChE) inhibition in hyperglycemic and stressogenic effects of monocrotophos in rats. Oral administration of monocrotophos (1.8 mg/kg b.w., 1/10 LD(50)) caused reversible hyperglycemia in rats with peak increase occurring at 2 h following administration. The hyperglycemic outcome at 2 h was accompanied by significant inhibition of acetylcholinesterase (AChE) activity in brain (84%), adrenal (68%) and liver (53%) and stressogenic effects as revealed by marked increase in plasma corticosterone (102%) and liver tyrosine aminotransferase (TAT) (104%) activity. At 4 h following administration, there was normalization of hyperglycemia and hypercorticosteronemia, marginal attenuation of liver TAT activity and marked increase in liver glycogen content, without spontaneous reactivation of AChE activity in the organs studied. Interestingly, pre-treatment of rats with acetylcholine (ACh) receptor antagonists-atropine sulfate and methyl atropine nitrate offered significant protection against hyperglycemia, hypercorticosteronemia and increased liver TAT activity induced by monocrotophos. Our results clearly demonstrate the involvement of AChE inhibition in hyperglycemia and stressogenic effects of monocrotophos in rats following acute exposure. Protection offered by both, general and peripheral ACh antagonists provide further evidence for the involvement of peripheral AChE inhibition in the monocrotophos-induced effects.

Topics: Acetylcholinesterase; Adrenal Glands; Animals; Atropine; Atropine Derivatives; Blood Glucose; Brain; Cholinergic Antagonists; Cholinesterase Inhibitors; Corticosterone; Glycogen; Hyperglycemia; Liver; Male; Monocrotophos; Rats; Rats, Inbred Strains; Receptors, Cholinergic; Stress, Psychological; Tyrosine Transaminase

The aim of this study was to assess the role of cholinergic transmission in the paraventricular nucleus of the hypothalamus (PVN) and carotid body receptors in mediating a rise in plasma glucose levels in response to hemorrhagic hypotension in rats. Methylatropine (1x10(-9) mol) or 0.15 M NaCl (0.2 microl) was injected into the PVN of Wistar rats weighing 250-300 g bearing a chronic jugular catheter for blood sampling and hemorrhage (1.2 ml/100 g/2 min). Polyethylene cannulae (PE-10) were inserted into the left femoral artery for cardiovascular monitoring. In the other experimental protocol, hemorrhage was performed on rats submitted to bilateral carotid receptor denervation (H-CD). The results show that the hyperglycemic response to hemorrhage was decreased by either methylatropine (H-MA) treatment or bilateral carotid receptor denervation (10.3+/-0.4 mM, control, n=15 vs. 7.7+/-0.2 mM, H-MA, n=12, and 7.6+/-0.3 mM, H-CD, n=5, p<0.01). Furthermore, methylatropine did not affect the recovery of blood pressure after hemorrhage-induced hypotension, suggesting that the metabolic and pressor adjustments have different efferent pathways. Our data demonstrate that cholinergic input from the PVN and carotid receptors (chemo- and/or baroreceptors) might participate in the same neural pathway activated by hemorrhage-induced hypotension that produces hyperglycemia.

Topics: Animals; Atropine Derivatives; Blood Glucose; Blood Pressure; Carotid Arteries; Carotid Body; Denervation; Heart Rate; Hemorrhage; Hyperglycemia; Male; Microinjections; Models, Biological; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Sodium Chloride; Statistics as Topic; Time Factors

Anesthesia affects general hemodynamics and regulation of organ perfusion. We used colored microspheres to measure pancreatic islet blood flow in conscious rats at two time points, during either hyperglycemia or hypoglycemia. This method, using black and green microspheres, was validated by comparison with previous microsphere experiments and by lack of effect of a nonmetabolizable glucose analog, 3-O-methylglucose, on islet perfusion. Basal and glucose-stimulated islet blood flow levels were similar in pentobarbital sodium-anesthetized and conscious rats. However, the basal distribution of pancreatic blood flow was altered by anesthesia (fractional islet blood flow 5.8 +/- 0.4% in conscious rats, 7.9 +/- 0.8% in pentobarbital-anesthetized rats, P < 0.05). Insulin-induced hypoglycemia significantly increased whole pancreatic blood flow in conscious rats, whereas islet blood flow remained unchanged and fractional islet blood flow was decreased (5.8 +/- 0.5% in the basal state, 4.2 +/- 0.4% during hypoglycemia, P < 0.001). Methylatropine pretreatment significantly increased islet blood flow during hypoglycemia by 181%. This result suggests that prevention of hypoglycemia-induced increase in islet perfusion may be mediated, at least in part, by a cholinergic, vagal muscarinic mechanism.

Topics: 3-O-Methylglucose; Anesthesia; Animals; Atropine Derivatives; Color; Hyperglycemia; Hypnotics and Sedatives; Hypoglycemia; Hypoglycemic Agents; Insulin; Islets of Langerhans; Male; Microspheres; Pentobarbital; Rats; Rats, Sprague-Dawley; Regional Blood Flow