Udelsman R, Li D G, Stagg C A, Gordon C B, Kvetnansky R
Laboratory of Endocrine Surgery, Johns Hopkins Hospital, Baltimore, MD 21287-5674.
Surgery. 1994 Aug;116(2):177-82.
Surgical stress results in catecholamine secretion and selective induction of the major heat shock protein (HSP70) in the adrenal gland and in the vasculature. The adrenal response is cortical-specific and corticotropin-dependent. The vascular response occurs in the smooth muscle and is corticotropin-independent. We previously suggested that the vascular response was associated with adrenergic receptor stimulation. Herein, we report a series of experiments designed to test the hypothesis that aortic HSP70 messenger RNA (mRNA) induction occurs as a direct and specific response to alpha 1-adrenergic receptor stimulation.
Acute and chronic indwelling central venous catheter models were developed in the Wistar rat through which the following agents were infused: the alpha 1 agonist phenylephrine (0.14 mg/kg), the beta agonist isoproterenol (0.8 mg/kg), the alpha 1 antagonist prazosin (1 mg/kg), prazosin followed by phenylephrine, or saline solution alone. Hemodynamic responses were monitored; catecholamines were measured by high-performance liquid chromatography; 60 minutes after infusion, the animals were killed, and the adrenal glands and aortas were assayed for HSP70 mRNA expression on Northern blots.
Alpha 1 stimulation with phenylephrine resulted in marked hypertension, a reflexive bradycardia, and marked induction of aortic HSP70 mRNA. This effect could be completely abolished when the alpha 1 antagonist prazosin was administered before phenylephrine treatment. The beta agonist isoproterenol failed to induce aortic HSP70. A significant catecholamine response only occurred after prazosin administration.
These studies show a functional interaction between alpha 1 receptor stimulation and vascular HSP mRNA induction.
手术应激会导致儿茶酚胺分泌，并选择性诱导肾上腺和血管中主要热休克蛋白（HSP70）的产生。肾上腺反应具有皮质特异性且依赖促肾上腺皮质激素。血管反应发生在平滑肌中，且不依赖促肾上腺皮质激素。我们之前曾提出血管反应与肾上腺素能受体刺激有关。在此，我们报告了一系列实验，旨在验证主动脉HSP70信使核糖核酸（mRNA）的诱导是对α1 - 肾上腺素能受体刺激的直接且特异性反应这一假说。
在Wistar大鼠中建立急性和慢性留置中心静脉导管模型，通过该模型输注以下药物：α1激动剂去氧肾上腺素（0.14毫克/千克）、β激动剂异丙肾上腺素（0.8毫克/千克）、α1拮抗剂哌唑嗪（1毫克/千克）、先给予哌唑嗪再给予去氧肾上腺素，或仅给予盐溶液。监测血流动力学反应；通过高效液相色谱法测量儿茶酚胺；输注60分钟后，处死动物，并在Northern印迹法上检测肾上腺和主动脉中HSP70 mRNA的表达。
用去氧肾上腺素进行α1刺激导致明显的高血压、反射性心动过缓以及主动脉HSP70 mRNA的显著诱导。在去氧肾上腺素治疗前给予α1拮抗剂哌唑嗪时，这种效应可被完全消除。β激动剂异丙肾上腺素未能诱导主动脉HSP70。仅在给予哌唑嗪后出现显著的儿茶酚胺反应。
这些研究表明α1受体刺激与血管HSP mRNA诱导之间存在功能相互作用。
