VARIATIONS IN THE PLATELET ARGININE NITRIC-OXIDE PATHWAY DURING THE OVARIAN CYCLE IN FEMALES AFFECTED BY MENSTRUAL MIGRAINE

Previous studies have reported the existence of an arginine/ nitric ox ide (NO) pathway and the involvement of a Ca2+, NADPH-dependent nitric oxide synthase enzyme (NOS) in the generation of NO in human platelet s. In the present research, we determined the rate of production of NO and cGMP in the cytosol of platelets stimulated by collagen in 20 fem ales with menstrual migraine (MM), (age range 24-40 years), assessed i n the follicular and luteal phases, interictally and ictally in the la tter period. The same patients were also assessed at mid-cycle. At the same time, the variations in the collagen response of platelets were evaluated. Moreover, these parameters were determined in the same peri ods in 20 age-matched control females and in 20 females affected by no n-menstrually related migraine (nMM). The collagen-stimulated producti on of NO in the cytosol of the platelet cytosol was significantly high er in migraine patients with MM than in the control subjects. In MM pa tients, the increase was greater in the luteal phase of the cycle than during the follicular phase (p<0.005). A rise in NO production in pla telets was also present, although to a lesser extent, in females affec ted by nMM compared to the healthy females, but this rise was most evi dent at ovulation (p<0.001). A slight but significant increase was als o observed at mid-cycle in control women, but this increase did not re ach the values determined in the migraine groups (p<0.02). NO producti on in platelets stimulated by collagen was significantly increased dur ing attacks with respect to the interictal period in both patient grou ps. Similar variations were observed in the production of cGMP in MM a nd nMM patients. The increase in NO production was accompanied by a de crease in platelet aggregation in the migraine groups compared with th e control group; this decrease was most evident at mid-cycle in nMM pa tients and in the luteal phase in MM patients. These data suggest an a ctivation of the L-arginine/NO pathway in MM and nMM patients which co uld explain the modifications in the platelet response to collagen evi denced in migraine-free periods and during attacks. The activation of this pathway is more accentuated in the luteal phase in MM patients, a nd this could be the cause of the increased susceptibility to migraine attacks in perimenstrual and menstrual periods in these patients.