Glyceryl trinitrate treatment up-regulates soluble guanylyl cyclase in rat dura mater.
Nitric oxide (NO) is a key molecule in vascular headaches and the dura mater has been implicated as a tissue where vascular headache develops. Here we demonstrate expression, enzyme activity and cellular distribution of the intracellular receptor for NO, soluble guanylyl cyclase (sGC), in rat dura mater. Subcutaneous treatment of rats with the NO-donor glyceryl trinitrate (GTN) induced an increase of sGC expression and activity in dural blood vessels after 20-30 min. It has previously been shown that GTN induces headache in normal subjects after 20-30 min. Our findings suggest that an up-regulation of the NO target enzyme contributes to the pathogenesis of GTN-induced headache explaining the subacute rather than acute onset of symptoms.
Behrends
S
S
Institut für Experimentelle und Klinische Pharmakologie, Universität Hamburg, Martinistrasse 52, D-20251 Hamburg, Germany.
Knyihár-Csillik
E
E
Kempfert
J
J
Scholz
H
H
Csillik
B
B
Vécsei
L
L
D000818:Animals; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000648:ultrastructure; D005260:Female; D006162:Guanylate Cyclase / Q000032:analysis / Q000378:metabolism*; D006261:Headache / Q000378:metabolism; D008297:Male; D016253:Microscopy, Immunoelectron; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D006162:Guanylate Cyclase; D005996:Nitroglycerin