Involvement of calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in the pial artery dilatation elicited by cortical spreading depression.
The aim of the present study was to examine whether the initial transient arterial dilatation during cortical spreading depression (CSD) was mediated by the release of calcitonin gene-related peptide (CGRP) and/or nitric oxide (NO). This question is of interest as the initial phase of CSD appears to be a model of events occurring during functional hyperemia and during the first period of classic migraine. Using an open cranial window technique, pial arterial diameter in the parietal cortex of cats was recorded with an image splitting method. Employing micropuncture technique, perivascularly applied CGRP8-37 did not alter the resting diameter of pial arteries but antagonized concentration dependently (5 x 10(-9)-10(-6) M) the dilatation (35%) due to 5 x 10(-8) M CGRP. NG-Nitro-L-Arginine (NOLAG, 10(-4) M) also had no effect on resting diameter of pial arteries, indicating that their resting tone is neither mediated by a continuous release of CGRP nor of NO. CSD was triggered by a remote intracortical injection of KCl (150 mM) and recorded by a microelectrode placed adjacent to the artery under investigation. CSD elicited a transient negative DC shift which was accompanied by a peak dilatation of 44 +/- 5.2% (S.E.M.). This dilatation was reduced by approximately 50% during topical application of 10(-7) M CGRP8-37 and 10(-4) M NOLAG each. A 75% inhibition of the CSD-induced dilatation was found during simultaneous application of both compounds. These data indicate that the initial dilatation during CSD is mediated, at least in part, by a release of CGRP and NO.(ABSTRACT TRUNCATED AT 250 WORDS)
Wahl
M
M
Dept. Physiology, University of Munich, Germany.
Schilling
L
L
Parsons
A A
AA
Kaumann
A
A
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010446:Peptide Fragments / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014664:Vasodilation / Q000502:physiology*
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D019335:Nitroarginine; D009569:Nitric Oxide; D011189:Potassium Chloride; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide