The Study Of Triggering Autorhythmicity Of Rat Aortic Ring And Its Mechanism And PMQ Ameliorated Glucose And Lipid Metabolic Disorders And Vascular Endothelial Dysfunction In GK Rats

Partâ… The study of triggering autorhythmicity of rat aortic ring and its mechanismObjective: To investigate the mechanisms of inducing the autorhythmicity in isolated rat thoracic aorta. Methods: SD rats thoracic aortic rings were prepared and equilibrated under resting tension for 1.5-2 h: 1) Observed the probability of the autorhythmicity inducing by various interventions including :â‘ Administered methoxamine (METH) (10μM);â‘¡high potassium once(60 mM);â‘¢high potassium twice;â‘£high potassium once for five minutes, then administered METH;⑤high potassium twice for five minutes, then administered METH;â‘¥METH after the endothelium was removed by rubbing the luminal;⑦METH after pretreatment with L-NMMA(100μM);⑧METH after administering high potassium twice without cleaning adhering connective tissue. 2)Reduced the basic tension to 80%, 60% 40%, 20% 0%, -20% of the original, then increased it back to 40%, observe the effects of the change of basic tension on the frequency of the autorhythmicity. 3)Observed the effects of nifedipine (0.01, 0.03, 0.1μM), nitroprusside-Na (0.001, 0.003, 0.01μM ), phentolamine (0.01, 0.03, 0.1μM) on the frequency of the autorhythmicity. Results:â‘ The probabilities of inducing the autorhythmicity of each interventions were 10%, 6.2%, 9.2%, 31.2%, 83.5%, 78.6%, 46.7%, 76.9% respectively;â‘¡The frequency of the autorhythmicity was uninfluenced by the change of the basic tension when the basic tension was above the resting tension. But when he basic tension was below the resting tension, the frequency of the autorhythmicity decreased significantly until it disappears. Though increased the basic tension at that time, the autorhythmicity does not appear again.â‘¢nifedipine,nitroprusside-Na and phentolamine significantly decreased the frequency of the autorhythmicity. Conclusion: 1) The injury of the endothelium facilitated the appearance of autorhythmicity, intact endothelium could prevent the appearance of autorhythmicity. 2) The vascular endothelium-derived NO is one of the mechanisms preventing the appearance of autorhythmicity. 3) A proper basic tension was a necessary for inducing the autorhythmicity. The frequecy of autorhythmicity was not directly related to the basic tension. 4)The autorhythmicity was related to the Ca²⁺ and calcium channel, adrenergic receptorαand the vascular endothelium-derived NO.Partâ…¡PMQ ameliorated glucose and lipid metabolic disorders and vascular endothelial dysfunction in GK ratsObjective: To observe the effects of pentamethylquercetin (PMQ) on glucose and lipid metabolism and endothelial function in GK rats. Methods: Wistar rats were taken as the normal control group. According to the fasting glucose level, GK rats were randomly divided into the 5 groups: GK group(diabetic model group); PMQ intervened goups (PMQ 2.5, 5.0, 10.0 mg/kg); positive control groups; Rosiglitazone group(Ros 5 mg/kg). All rat groups were treated for 16 consecutive weeks. Body weight, consumption of food and water were recorded. Fasting and fed glucose, fed TG , TC , HDL-C and insulin levels were measured. Oral glucose tolerance test were performed periodically before experiment and at the 8th and 16th week after treatment. Thoracic aortic rings from rats were isolated and pre-contracted by METH(100μM). Then the cumulative concentration-response curves for carbachol (0.1,0.3,1,3,10μM) were obtained. Results: Compared with Wistar rats, GK rats showed some disorders including polydipsia, polyphagia and emaciation; a little higher fasting blood glucose, greatly increased postprandial blood glucose, markedly impaired glucose tolerance; higher postprandial TC; significantly elevated fasting insulin, lower postprandial insulin; impaired endothelium-dependent relaxation. PMQ intervention improved polydipsia, polyphagia and emaciation, significantly ameliorated glucose intolerance, reduced postprandial blood glucose, lowered fasting insulin levels, decreased fed TG and TC levels slightly in comparison to to GK model group. PMQ also could ameliorated vascular endothelial dysfunction in GK rats. Conclusion: PMQ ameliorated glucose and lipid metabolism and vascular endothelial dysfunction in GK rats.