Lang C H, Dobrescu C, Hargrove D M, Bagby G J, Spitzer J J
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Am J Physiol. 1988 Feb;254(2 Pt 1):E193-200. doi: 10.1152/ajpendo.1988.254.2.E193.
Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of [6-3H]- and [U-14C]glucose before and for 4 h after either a bolus injection (300 ng/kg) or a constant infusion (20 or 220 ng.min-1.kg-1) of PAF. The bolus injection of PAF produced a 30% decrease in blood pressure by 5 min that returned to control levels by 30 min. Increased plasma glucose (40%) and lactate (150%) levels after injection of PAF were also transient. In contrast, the bolus injection of PAF elevated the rate of glucose appearance (Ra; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose (28, 150%) and glucose Ra (20, 60%) throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. In a separate group of experiments a complete adrenergic blockade, produced by the constant infusion of propranolol and phentolamine, completely prevented PAF-induced increases in glucose kinetics and the hyperglucagonemia.(ABSTRACT TRUNCATED AT 250 WORDS)
血小板活化因子(PAF)被假定为内毒素许多早期血流动力学效应的介质。本研究的目的是确定体内给予PAF是否会引起全身葡萄糖代谢改变,从而模拟内毒素血症时所见的情况。通过在慢性插管清醒大鼠中持续输注[6-³H]-和[U-¹⁴C]葡萄糖,在单次注射(300 ng/kg)或持续输注(20或220 ng·min⁻¹·kg⁻¹)PAF之前及之后4小时评估葡萄糖动力学。单次注射PAF后5分钟血压下降30%,30分钟时恢复至对照水平。注射PAF后血浆葡萄糖(40%)和乳酸(150%)水平升高也是短暂的。相比之下,单次注射PAF使葡萄糖生成率(Ra)升高1.5小时(44%)。较低的PAF输注速率使血压下降11%至104 mmHg,而较高输注速率使血压下降34%至77 mmHg。在整个4小时输注期间,两种PAF输注速率均以剂量相关方式使血浆葡萄糖(分别为28%、150%)和葡萄糖Ra(分别为20%、60%)升高。在整个输注期间,PAF输注还诱导血浆胰高血糖素和儿茶酚胺水平呈剂量相关增加。在另一组实验中,通过持续输注普萘洛尔和酚妥拉明产生的完全肾上腺素能阻断,完全阻止了PAF诱导的葡萄糖动力学增加和高胰高血糖素血症。(摘要截选至250字)