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The Pharmacology of Autonomic Failure: From Hypotension to Hypertension.
Pharmacological Reviews ( IF 21.1 ) Pub Date : 2016-12-25 , DOI: 10.1124/pr.115.012161
Italo Biaggioni 1
Affiliation  

Primary neurodegenerative autonomic disorders are characterized clinically by loss of autonomic regulation of blood pressure. The clinical picture is dominated by orthostatic hypotension, but supine hypertension is also a significant problem. Autonomic failure can result from impairment of central autonomic pathways (multiple system atrophy) or neurodegeneration of peripheral postganglionic autonomic fibers (pure autonomic failure, Parkinson's disease). Pharmacologic probes such as the ganglionic blocker trimethaphan can help us in the understanding of the underlying pathophysiology and diagnosis of these disorders. Conversely, understanding the pathophysiology is crucial in the development of effective pharmacotherapy for these patients. Autonomic failure patients provide us with an unfortunate but unique research model characterized by loss of baroreflex buffering. This greatly magnifies the effect of stimuli that would not be apparent in normal subjects. An example of this is the discovery of the osmopressor reflex: ingestion of water increases blood pressure by 30-40 mm Hg in autonomic failure patients. Animal studies indicate that the trigger of this reflex is related to hypo-osmolality in the portal circulation involving transient receptor potential vanilloid 4 receptors. Studies in autonomic failure patients have also revealed that angiotensin II can be generated through noncanonical pathways independent of plasma renin activity to contribute to hypertension. Similarly, the mineralocorticoid receptor antagonist eplerenone produces acute hypotensive effects, highlighting the presence of non-nuclear mineralocorticoid receptor pathways. These are examples of careful clinical research that integrates pathophysiology and pharmacology to advance our knowledge of human disease.

中文翻译:

自主神经功能衰竭的药理学:从低血压到高血压。

在临床上,原发性神经退行性自主神经失调的特征是失去自主调节血压的能力。临床表现主要是体位性低血压,但是仰卧位高血压也是一个重要的问题。自主神经衰竭可能是由于中央自主神经通路受损(多系统萎缩)或周围神经节后自主神经纤维神经变性(纯自主神经衰竭,帕金森氏病)引起的。诸如神经节阻滞剂甲氨苄草胺之类的药理探针可以帮助我们理解这些疾病的潜在病理生理学和诊断。相反,了解病理生理学对于这些患者有效药物治疗的发展至关重要。自主神经衰竭患者为我们提供了一个不幸但又独特的研究模型,其特征是压力反射缓冲液的丢失。这极大地放大了在正常受试者中不明显的刺激效果。这方面的一个例子是发现了渗透压调节器的反射:摄入水会使自主神经衰竭患者的血压升高30-40 mm Hg。动物研究表明,这种反射的触发与门静脉循环中的低渗透压有关,该渗透压涉及瞬时受体潜在的香草酸4受体。自主神经衰竭患者的研究还表明,血管紧张素II可以通过非经典途径产生,而与血浆肾素活性无关,从而导致高血压。同样,盐皮质激素受体拮抗剂依普利农产生急性降压作用,突出了非核盐皮质激素受体途径的存在。这些是经过仔细的临床研究的例子,这些研究结合了病理生理学和药理学,以增进我们对人类疾病的认识。
更新日期:2019-11-01
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