MODIFICATION OF VASOCONSTRICTOR RESPONSES IN CEREBRAL BLOOD-VESSELS BY LESIONING OF THE TRIGEMINAL NERVE - POSSIBLE INVOLVEMENT OF CGRP

The functional role of the trigeminal system has been addressed in exp eriments on the cortical surface of alpha-chloralose anaesthetized cat s. Application of calcitonin gene-related peptide (CGRP) caused a conc entration-dependent increase in arteriolar calibre by 38 +/- 5% (n = 8 ) with an IC50 of 2 nM. Cerebral veins did not relax upon CGRP adminis tration (n = 12). Substance P (SP) was less potent but showed dilatati on of both arterioles (21 +/- 4%) and veins (16 +/- 4%). The cerebrova scular trigeminal system was investigated alter chronic (14 days) surg ical lesion of the trigeminal nerve with the concomitant disappearance of perivascular CGRP/SP immunoreactive nerves. The cortical arteriola r responses to subarachnoid microinjections of acidic (pH 6.8) and bas ic CSF (pH 7.6) as well as noradrenaline (10(-4) M), neuropeptide Y (1 0(-7) M), prostaglandin F-2 alpha (10(-6) M), barium chloride (10(-4) M), and autologous blood (5 mu l) were examined in anaesthetized cats with lesions of the trigeminal nerve, and were compared with their eff ects in sham-operated animals. The magnitude of the vasodilator and va soconstrictor responses to these agents was unaffected by trigeminal l esions. However, duration of the vasoconstriction produced by basic CS F, but not the vasodilatation to acidic CSF, was markedly prolonged by trigeminal lesions (from 0.8 +/- 0.1 min to 2.2 +/- 0.3 min, p < 0.01 ). Also, the vasoconstrictor responses to noradrenaline, prostaglandin F-2 alpha barium chloride, and autologous blood were significantly pr olonged, while the maximum contractile effect to each agent was simila r in lesioned as in sham-operated controls. The effects of CGRP, SP, a nd neurokinin A (NKA) have been examined on isolated cerebral arteries in vitro. Different CGRP analogues induced a strong relaxation with n o difference in I-max (85 - 96%) or pD(2), values (8.65 - 9.12). NKA i nduced a stronger relaxation than SP (I-max: 33% and 13%, respectively ). SP was more potent than NKA (pD(2): 8.7 and 7.7, respectively). Cap saicin, a substance which selectively causes the release of stored sen sory neuropeptides (CGRP, SP, NKA), caused in vitro relaxation of prec ontracted arteries. This relaxation was not affected by the neurokinin blocker spantide, but shifted towards higher capsaicin concentrations by the CGRP antagonist CGRP(8-37). Thus, in this preparation CGRP rat her than a neurokinin (SP/NKA) is responsible for the capsaicin-induce d dilatations.