Nitric oxide sensitivity in patients with autonomic neuropathy
Research type
Research Study
Full title
Evaluation of nitric oxide and catecholamine sensitivity in patients with autonomic neuropathy
IRAS ID
186319
Contact name
Joseph Cheriyan
Contact email
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
The most predominant symptom suffered by patients with autonomic neuropathy is postural hypotension which can result in considerable morbidity and serious injury. The mechanism of postural hypotension is thought to be a loss of sympathetic vasoconstrictor responses in the legs to standing, which allows blood to pool, impedes cardiac output, and therefore blood pressure falls.
One of the key mediators of maintaining vascular tone in blood vessels is nitric oxide which is produced by endothelial and neuronal cells. Research has shown that in autonomic neuropathy, there is a loss of nitrergic neurons that respond to nitric oxide supplying the resistance blood vessels, which would effectively result in an increase of peripheral vascular resistance and thus increased blood pressure. While human studies have demonstrated that resting nitric oxide production in the microvasculature is due to neuronal nitric oxide synthase (nNOS) activity, the exact location of nNOS is not known.
The basis of this application is built on a series of experiments developed to investigate the physiological response to basal and stimulatory release of nitric oxide in autonomic neuropathy patients. Our hypothesis is that there is a reduced basal nNOS nitric oxide production in autonomic neuropathy as well as in dysautonomia (a state of impaired autonomic function but no neuropathy). The pilot data obtained in this study from these patients will hopefully help doctors determine which type of treatment is best for newly diagnosed autonomic neuropathy patients in the future, and in developing new treatments.
REC name
North of Scotland Research Ethics Committee 2
REC reference
15/NS/0079
Date of REC Opinion
1 Sep 2015
REC opinion
Further Information Favourable Opinion