Retinal vascular caliber and migraine: the Blue Mountains Eye Study

OBJECTIVE: To assess whether migraine is associated with retinal microvascular caliber. BACKGROUND: Migraine is believed to be associated with vascular disease, but few studies have investigated the relationship between structural microvascular changes and migraine. DESIGN: Population-based cross-sectional study. METHODS: Participants in the Blue Mountains Eye Study follow-up (1997 to 1999, n = 2,335, aged 54+) had retinal photographs taken. A computer-assisted method was used to measure average retinal arteriolar and venular diameters and calculate the arteriole-to-venule ratio. History of migraine was recorded by interview using International Headache Society criteria (1988). RESULTS: Subjects giving a history of migraine without aura (n = 128) had narrower retinal arterioles than subjects giving a history of migraine with aura (n = 182) or subjects with no migraine history (n = 1619). After multivariate adjustment, mean retinal arteriolar diameter was 4.3 microm (95% confidence interval 0.5, 8.1) narrower in subjects reporting migraine without aura as compared to subjects with no migraine. CONCLUSIONS: Individuals with a history of migraine without aura were more likely to have slightly narrower retinal arteriolar caliber than individuals without migraine. This relationship was not present for migraine with aura. These data support the hypothesis that microvascular disease may be associated with certain types of migraine.     

5-HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo

Objective

Serotonin (5-HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5-HT₇ receptors mediate arteriolar dilation to 5-HT in skeletal muscle microcirculation.

Methods

Cremaster muscles of isoflurane-anesthetized male Sprague-Dawley rats were prepared for in vivo microscopy of third- and fourth-order arterioles and superfused with physiological salt solution at 34°C. Quantitative real-time PCR (RT-PCR) was applied to pooled samples of first- to third-order cremaster arterioles (2–4 rats/sample) to evaluate 5-HT₇ receptor expression.

Results

Topical 5-HT (1–10 nmols) or the 5-HT_1/7 receptor agonist, 5-carboxamidotryptamine (10–30 nM), dilated third- and fourth-order arterioles, responses that were abolished by 1 μM SB269970, a selective 5-HT₇ receptor antagonist. In contrast, dilation induced by the muscarinic agonist, methacholine (100 nmols) was not inhibited by SB269970. Serotonin (10 nmols) failed to dilate cremaster arterioles in 5-HT₇ receptor knockout rats whereas arterioles in wild-type litter mates dilated to 1 nmol 5-HT, a response blocked by 1 μM SB269970. Quantitative RT-PCR revealed that cremaster arterioles expressed mRNA for 5-HT₇ receptors.

Conclusions

5-HT₇ receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5-HT-induced hypotension, in vivo.