UNLABELLED: 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. IN CONCLUSION: (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.
UNLABELLED: 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. IN CONCLUSION: (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.
Authors: Shan H Siddiqi; Natalia K Abraham; Christopher L Geiger; Morvarid Karimi; Joel S Perlmutter; Kevin J Black Journal: Front Pharmacol Date: 2016-01-06 Impact factor: 5.810