Rat aorta relaxation induced by the venom of Poecilotheria regalis involves the activation of the NO/cGMP pathway

Abstract Spider venoms are widely recognized as a new emerging source of potential research tools, pesticides, drug leads, and therapeutic agents. Some studies suggest that these venoms may contain interesting vasodilator compounds with potential therapeutic applications. In the present study, the vasodilator activity of the venom of Poecilotheria regalis was evaluated in isolated rat aortic rings. This venom induced an endothelium-dependent vasodilation [EC 50 value was 5.52 (4.18–7.32) μg protein/ml with an E max  = 103.4 ± 3.8%]. While the percentage of vasodilation induced by the venom was significantly diminished in the presence of a nitric oxide synthase inhibitor (L-NAME), it remained unaltered in the presence of suramin, a P2-purinergic receptor antagonist. Moreover, the vasodilator activity of the venom was not affected after boiling bath incubation, but was significantly decreased under reducing conditions. Additionally, venom composition was analyzed by reverse-phase chromatography and MALDI-TOF mass spectrometry, and two fractions were obtained, referred to as peptidic and non-peptidic fractions. Interestingly, both fractions induced vasodilation in isolated rat aortic rings. The results of this study showed that the venom of P. regalis induces a concentration-dependent vasodilation in rat aorta that was endothelium-dependent and involves the activation of NO/cGMP pathway. These results suggest that the venom contains a combination of both peptidic and non-peptidic vasodilator components. This study provides pharmacological data that suggest that P. regalis venom may be an important source of peptidic and non-peptidic vasodilator compounds.