tetrodotoxin and Subarachnoid-Hemorrhage

Serotonin released from platelets has been suggested as one substance causing the vasospasm following subarachnoid hemorrhage. We studied whether such serotonin is able to constrict pial vessels.. We studied the uptake of serotonin in pial perivascular nerves by immunohistochemistry. We measured the contractile response in rat basilar artery after in vitro incubation with serotonin and during electrical field stimulation of perivascular nerves following experimental subarachnoid hemorrhage.. After incubation with serotonin, electrical field stimulation caused a tetrodotoxin- and ketanserin-blockable contractile response. We observed no such response in vessels from rats treated with 6-hydroxydopamine or after blockade of serotonin uptake. After subarachnoid hemorrhage, a pronounced network of serotonin-immunoreactive nerve fibers was demonstrated in the vessel wall. In vessels from control rats, no serotonin fibers were seen, and in vessels from 6-hydroxydopamine-treated animals with subarachnoid hemorrhage only a few such fibers were seen. Electrical field stimulation of the basilar artery from rats tested 2 or 16 hours (but not 10 minutes or 24 hours) after subarachnoid hemorrhage showed contractile responses that were prevented by tetrodotoxin, ketanserin, and prior 6-hydroxydopamine treatment.. Our study demonstrates a capacity of the perivascular sympathetic nerves to take up serotonin both in vitro and during the early phase of subarachnoid hemorrhage. Such uptake may help to remove excess serotonin from the subarachnoid space. Only if serotonin is subsequently released upon nerve activation may minor smooth muscle contraction develop.

Topics: Animals; Basilar Artery; Electric Stimulation; Ischemic Attack, Transient; Ketanserin; Male; Oxidopamine; Paroxetine; Piperidines; Rats; Rats, Inbred Strains; Serotonin; Subarachnoid Hemorrhage; Sympathetic Nervous System; Tetrodotoxin; Vasoconstriction

We studied isolated basilar artery segments from a rabbit model of chronic cerebrovasospasm. Autologous blood placed around the basilar artery of rabbits killed 1, 2, 3, 4, 5, 6, 7, or 9 days later caused narrowing of the segments with a biphasic time course. The first (immediate) phase was reversed by intra-arterial papaverine; the second phase exhibited an increasing component of narrowing that was papaverine-insensitive. Based on the passive force/length curves, basilar artery segments became increasingly stiff over 9 days. By contrast, the segments' contractility decreased. Responses of the basilar artery segments were greater over the first few days, but then became less than that of saline-injected controls. Contractions in response to norepinephrine and potassium were reduced. Endothelium-based acetylcholine-induced vasodilation progressively diminished, as did the response to sympathetic nerve stimulation. There was a negative correlation between artery wall stiffness and contractility. The papaverine-insensitive component of angiographic narrowing correlated directly with loss of contractility and with artery wall stiffness. These results are consistent with the conclusion that increased artery wall stiffness is a primary determining factor in the arterial narrowing of chronic cerebrovasospasm.

Topics: Acetylcholine; Animals; Basilar Artery; Cimetidine; Epinephrine; Histamine; In Vitro Techniques; Ischemic Attack, Transient; Papaverine; Prazosin; Rabbits; Serotonin; Subarachnoid Hemorrhage; Tetrodotoxin; Vasoconstriction