Barietin, a snake venom vascular endothelial growth factor from puff adder Bitis arietans venom, increases the heart rate with minor effect on blood pressure in rats

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Barietin, a snake venom vascular endothelial growth factor from puff adder Bitis arietans venom, increases the heart rate with minor effect on blood pressure in rats

ABSTRACT

Snake venom vascular endothelial growth factors (svVEGFs) are homodimeric proteins comprising two equal subunits bound by two intermolecular disulfide bonds. The main biological effects of svVEGFs are local vasodilatation, increasing of vascular permeability, and hypotension. Barietin, a svVEGF purified from the venom of puff adder Bitis arietans, differs from other representatives of this toxin family by its shortened C-terminal amino acid sequence. No data about barietin effects on hemodynamics are available. Studying those in rats we found that barietin at a dose of 1 mg/kg significantly increased heart rate, exerting only a minor influence on blood pressure. In this respect, it differs from other svVEGFs having a significant effect on blood pressure. We aimed to find the barietin active fragment which may be responsible for its tachycardic activity. Because in literature the fragments corresponding to the so-called loop 1 of VEGF-A (a mammalian homologue of barietin) manifested some affinity to VEGF receptors, we synthesized a peptide homologous to this loop comprising barietin fragment 24-36, with two Cys residues added at the N- and C-termini to form a disulfide. At intravenous injection at a dose of 5 mg/kg, it showed a tendency to increase heart rate without any significant effect on blood pressure, thus demonstrated a trend to reproduce the effect of barietin. So, barietin is the first svVEGF which increases the heart rate without substantial effect on the blood pressure, with its fragment demonstrating a trend for a similar activity.
Severyukhina, M. S., Osipov, A. V., Ismailova, A. M., Shaykhutdinova, E. R., Dyachenko, I. A., Starkov, V. G., Ziganshin, R. H., Timofeev, N. D., Murashev, A. N., Tsetlin, V. I., & Utkin, Y. N. (2026). Barietin, a snake venom vascular endothelial growth factor from puff adder Bitis arietans venom, increases the heart rate with minor effect on blood pressure in rats. Toxicon, 109275. https://doi.org/10.1016/j.toxicon.2026.109275