In Vivo Effect of Calcitonin Gene Related Peptide on Middle Cerebral Artery Blood Flow Velocity In Humans

Abstract

A double blind, placebo controlled, escalating dose study was undertaken in five healthy, conscious volunteers to investigate the effects of human synthetic alpha calcitonin gene-related peptide (CGRP) on middle cerebral artery (MCA) blood flow velocity using transcranial Doppler sonography. During placebo infusion, there was no significant change in any of the parameters studied. During CGRP infusion, all subjects showed flushing of the face and neck. Infusion of CGRP caused a significant increase in arterial pulse pressure and heart rate and a fall in diastolic and mean arterial blood pressure when compared to baseline. Peak and mean MCA velocity did not change significantly. There was a significant increase in pulsatility index though interpretation of this was confounded by the central systemic effects of CGRP. The observed haemodynamic changes may be explained by a prompt sympathetic nervous system response in order to maintain mean arterial blood pressure. Our data suggest that if cerebral vasodilatation had occurred, it was not associated with increased blood flow as an increase in MCA velocity might have been expected. An alternative explanation is that, at the doses employed, CGRP did not cause dilatation of normal cerebral vessels in healthy subjects. This does not however exclude the fact that CGRP may cause dilatation of a spastic artery as seen in cerebral vasospasm following subarachnoid haemorrhage.