Altered Serum Levels of Renin‐Angiotensin System Markers in Migraine

Abstract

Objective.-To compare the serum levels of renin-angiotensin system (RAS) components between patients with migraine and healthy controls, and to evaluate whether these levels are associated with migraine severity. We hypothesized that migraine would be associated with the activation of the inflammatory arm of the RAS, possibly leading to increased levels of angiotensin (Ang) II. Background.-Recent studies have proposed the use of drugs that interfere with RAS, a hormonal system primarily implicated in blood pressure regulation, as a prophylactic strategy for migraine. However, no previous studies have directly assessed RAS components in migraine. Methods.-This was a cross-sectional study involving 30 patients with episodic migraine who were in the interictal period and 20 healthy controls. This study was conducted at Hospital das Clínicas (Universidade Federal de Minas Gerais, Belo Horizonte, Brazil) outpatient clinic. Headache severity was evaluated using the Headache Impact Test, version 6 (HIT-6) and the Migraine Disability Test (MIDAS) questionnaires. Given that migraine is comorbid with mood disorders, depressive and anxious symptoms were evaluated using the Beck Anxiety and Depression Inventories (BDI and BAI), respectively. Clinical and demographic data were also collected. Serum levels of angiotensin-converting enzyme (ACE), ACE2, Ang II, and Ang (1-7) were measured by enzyme-linked immunosorbent assay. Results.-Patients with migraine and controls were comparable in age, body mass index, blood pressure, and depressive and anxious symptoms. Patients with migraine showed lower levels of ACE [

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“…It has also been associated to neurogenic inflammation, susceptibility to oxidative stress, ED, and neuromodulation of nociceptive transmission [ 26 ] all crucial processes in migraine pathophysiology as well. RAAS role in migraine mechanisms was also supported by the evidence of RAAS hyperactivation and higher angiotensin II levels in migraine patients [ 66 ]. Moreover, angiotensin receptors (AT1 and AT2) are expressed in the most important CNS loci involved in nociception and pain modulation, such as the anterior cingulated cortex, prefrontal cortex, thalamus, PAG, amygdala, nucleus accumbens and spinal cord [ 63 ].…”

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“…Beyond the classical role of RAS, recently it has been noticed that this system correlates with cancerogenesis, modulation of glucose-stimulated insulin secretion [27], metabolic syndrome [28], progression of diabetic retinopathy, age-related macular degeneration [29], diabetes comorbid depression [30], and even migraine [31]. RAS influences processes like proliferation, apoptosis, autophagy, migration, inflammation, oxidative stress, or angiogenesis [25].…”

“…As previously mentioned, the role of the RAS has two faces, pathological and physiological without which the proper functioning of the organism would not be possible. Scientific evidence suggests that the effects of angiotensins on the brain vary widely [18,22,31,[94][95][96]. Highest concentrations of AT1R are located in brain areas important in the regulation of body-fluid balance and blood-pressure maintenance.…”

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