Puritz R, Lightman S L, Wilcox C S, Forsling M, Bannister R
Brain. 1983 Jun;106 (Pt 2):503-11. doi: 10.1093/brain/106.2.503.
We showed previously that patients with progressive autonomic failure with multiple system atrophy (MSA) failed to excrete a water load while they were standing, suggesting abnormal postural regulation of vasopressin release. The rise of plasma arginine vasopressin (AVP) with upright posture is modulated by central dopamine and opioid receptors. Patients with MSA may have depletion of brain dopamine and opioid peptides. We measured the plasma levels of AVP in patients with MSA and control subjects during postural stimulation by head-up tilt and the inhibition of this rise in AVP by L-DOPA (dopamine precursor) and naloxone (opiate antagonist). Since L-DOPA and naxolone can alleviate hypotension, we also studied the effects of these agents on orthostatic hypotension. Plasma AVP concentration of normal subjects rose progressively over 90 min of head-up tilt and this postural rise in AVP was abolished by L-DOPA and naloxone. Patients with MSA had similar levels of AVP while horizontal. However, they showed a severely blunted postural AVP response since their levels rose to only 10 per cent of the rise in the normal subjects despite the additional stimulus to AVP secretion of considerable postural hypotension. They also showed no inhibition of AVP secretion by L-DOPA or naloxone. Naloxone did not alter the blood pressure of either group. Although L-DOPA did not change the blood pressure of normal subjects, it lowered it in patients with MSA both while they were horizontal and tilted.
(1) the postural stimulation of AVP release is blunted in MSA; (2) this postural rise in AVP is not inhibited by a dopamine agonist or opioid antagonist in MSA suggesting loss of dopaminergic and opioid pathways involved in AVP release; (3) endogenous opioids do not contribute to orthostatic hypotension in MSA; (4) patients with MSA are supersensitive to the hypotensive effects of an acute L-DOPA infusion.
我们之前表明，患有多系统萎缩（MSA）并伴有进行性自主神经功能衰竭的患者在站立时无法排出水负荷，提示血管加压素释放的姿势调节异常。血浆精氨酸血管加压素（AVP）随直立姿势的升高受中枢多巴胺和阿片受体调节。MSA患者可能存在脑内多巴胺和阿片肽耗竭。我们在通过头高位倾斜进行姿势刺激期间以及左旋多巴（多巴胺前体）和纳洛酮（阿片拮抗剂）对AVP升高的抑制作用过程中，测量了MSA患者和对照受试者的血浆AVP水平。由于左旋多巴和纳洛酮可缓解低血压状况，我们还研究了这些药物对直立性低血压的影响。正常受试者的血浆AVP浓度在头高位倾斜90分钟内逐渐升高，且这种AVP的姿势性升高被左旋多巴和纳洛酮消除。MSA患者在卧位时的AVP水平相似。然而，他们的姿势性AVP反应严重减弱，因为尽管姿势性低血压对AVP分泌有额外刺激，但他们的AVP水平仅升至正常受试者升高水平的10%。他们对左旋多巴或纳洛酮也无AVP分泌抑制作用。纳洛酮未改变两组的血压。虽然左旋多巴未改变正常受试者的血压，但它降低了MSA患者卧位和倾斜位时的血压。
（1）MSA患者中AVP释放的姿势刺激减弱；（2）MSA患者中AVP的这种姿势性升高不受多巴胺激动剂或阿片拮抗剂抑制，提示参与AVP释放的多巴胺能和阿片通路丧失；（3）内源性阿片类物质对MSA患者的直立性低血压无影响；（4）MSA患者对急性左旋多巴输注的降压作用超敏感。
