A new migraine medication could endanger people with chronic high blood pressure, according to research in mice.
The new migraine medications block the neuropeptide αCGRP (α calcitonin gene-related peptide). The very same peptide, which forms in the muscles during physical activity, protects the heart—which is vital for people with chronic high blood pressure.
αCGRP works in two different ways. It leads to inflammation and dilates the blood vessels right at the release point of the nerve cells, for example in the meninges, which can trigger migraine attacks. However, it has a completely different effect on the heart, the researchers found.
The scientists also found that active skeletal muscles release αCGRP. The blood transports it from the muscle to the heart where it inhibits the pathological heart remodeling that chronic high blood pressure causes.
“It is exactly the same for humans as it is for mice,” says study leader Johannes Vogel, professor at the University of Zurich’s Institute of Veterinary Physiology. “Physical activity and sport increase the blood plasma levels of αCGRP, which has a positive effect on the heart in patients with high blood pressure.”
The researchers compared normal mice to others with chronic high blood pressure, which were either sedentary or repeatedly and voluntarily ran in a running wheel. The study reveals that having normal concentrations of αCGRP in the blood plasma is vital and that the peptide is crucial for the positive effects of physical activity on the heart. αCGRP also provides the heart with extra protection, regardless of its antihypertensive properties in high doses.
“In the future, substances that activate the release of αCGRP or mimic its action could be used in hypertensive patients who can only be physically active to a very limited extent or in whom antihypertensive medications have little or no effect,” explains Vogel.
The research also brought another finding to light—long-term administration of αCGRP blockers in mice with chronic high blood pressure resulted in life-threatening cardiac dysfunction. Medications of this kind, which take a targeted approach to blocking the neuropeptide, have recently been approved for migraine prophylaxis. As the neuropeptide αCGRP in species from zebrafish to humans is very similar, it must be part of a key biological mechanism that works in the same way in different organisms.
According to Vogel, the results are therefore also relevant to humans: “αCGRP blockers should only be used for migraine prevention with the proviso that patients’ blood pressure is monitored regularly. Chronic high blood pressure should be added to the list of contraindications for the long-term use of αCGRP blockers.”
The research appears in Circulation Research.
Source: University of Zurich