The importance of substance P and calcitonin gene related peptide as vasodilator neuropeptide during acute phase of experimental posthemorrhagic vasospasm.
BACKGROUND
Several immunohistochemical studies conducted in the acute phase following SAH have demonstrated a marked depletion of certain peptides like Substance P (SP), Calcitonin Gene Related Peptide (CGRP) from the adventitia of perivascular nerves. The present experimental study was carried out with the aim of determining whether the depletion of these peptides could be a protection mechanism against the factors which sustain the vasospasm.


METHODS
To accomplish this goal, we administered specific antiserum to block the potential effect of neuropeptides (SP and CGRP) prior to SAH. Our study tried also to realize whether difference can be demonstrated between endothelium-dependent (SP) and endothelium-independent vasodilatory mechanisms (CGRP) during the acute phase ofvasospasm. Twenty-three rabbits were divided in 5 experimental groups: Group A included normal control animals, Group B included rabbits who received saline injection prior to SAH, Group C included animals who received preimmune serum, groups D and E included animals who received respectively antiserum against CGRP and against SP prior to SAH. The antisera were administered into the cisterna magna by means of percutaneous suboccipital puncture. After 15 minutes 1 ml of autologous non-heparinized blood was injected in the same way. After 20 minutes the animals were sacrificed by cardiac perfusion. The basilar artery was removed by means of transclival approach and it was included in Epon 812. Mean diameters and luminal areas of the arteries were measured with morphometric method on sections of 2-3 microm of thickness.


RESULTS
The results showed a reduced mean diameter and luminal areas in the group B comparing to normal controls of the group A. A marked vasospasm is mainly evident in group D and E. In group C the vasospasm is not significantly different from that of group B. No significant difference was demonstrated between group D and group E.


CONCLUSIONS
We can conclude that: 1) the marked depletion of neuropeptides in the early phases of vasospasm represents a functional phenomenon in order to reduce the effectiveness of spasmogenic stimula. In fact the inhibition of the activity of these neuropeptides worses the entity of the vasospasm. 2) During the acute phase of vasospasm the endothelium-dependent vasodilatory mechanism is still functioning. No significant difference in the entity of vasospasm has been demonstrated between inhibition of SP (endothelium-dependent) and CGRP (endothelium-independent). Inactivation of such a mechanism occurs during late phases.
Locatelli
M
M
Department of Neurosurgery, University of Milan, Ospedale Maggiore di Milano, Policlinico IRCCS, Italy.
D000818:Animals; D001488:Basilar Artery / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D011817:Rabbits; D012016:Reference Values; D013345:Subarachnoid Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology*; D014664:Vasodilation; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
D007106:Immune Sera; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide