The absolute indomethacin effect in some unilateral headaches may, at least partially, be cyclooxygenase inhibition-independent. Aspirin and indomethacin, for example, may inhibit the neurogenically induced plasma extravasation in rat dura mater. Given the putative involvement of trigeminal neuropeptides in the pathophysiology of these conditions, the influence of cyclooxygenase inhibitors (indomethacin, acetylsalicylic acid (ASA) and naproxen) has been studied upon substance P, calcitonin gene-related peptide and vasoactive intestinal peptide (VIP)-induced vasodilatation in PGF2a precontracted porcine ophthalmic arteries in vitro. None of the cyclooxygenase inhibitors significantly altered the effects of calcitonin gene-related peptide. The 10-10 mol/1 VIP-induced relaxation was inhibited significantly by all three cyclooxygenase inhibitors. Substance P-induced relaxation (from 10-10 to 10-8 mol/l) was enhanced by ASA and inhibited both by naproxen and, to a lesser extent, by indomethacin. The results suggest mainly that VIP-induced relaxations, particularly at lower concentrations, may be inhibited by all three cyclooxygenase inhibitors, and that naproxen, to a greater extent than aspirin or indomethacin, showed a tendency to inhibit vasodilatation induced by all peptides.
The Levels of Calcitonin Gene‐Related Peptide and Substance P in the Plasma of Rats with Traumatic Brain Injury and the Role of Neurogenic Inflammation in the Pathogenesis of TBI
