6). Snakes venoms contain peptides with structural and functional equivalents of mammalian NPs (ANP, BNP and CNP), which present dose-dependent hypotensive effects [10], [34] and [40]. In addition to natriuretic peptide studies, a 38-amino acid residues peptide (DNP) was isolated from the venom of Dendroaspis angusticeps (the green mamba snake), demonstrating properties that are similar to both

Ion Channel Ligand Library chemical structure human ANP and BNP [33]. Other NPs from snake venoms were identified from Lachesis muta (Lm-CNP), Bothrops jararacusu (Bj-CNP) and other snakes presenting a homologous structure for the human CNP [28] and [35]. The hypotensive effect of Coa_NP2, presented herein, occurred in association with a significant increase in plasma nitrite levels, corroborating with previously data suggesting that NPs are able to stimulate nitric oxide (NO) production [4]. Together, a NO-dependent hypotensive effect was identified with a peptide isolated

from the snake venom of Agkistrodon acutus [34], and it was shown that infusion of NP isolated from Crotalus durissus cascavella venom was responsible for the increased nitrite levels [10]. Thus, these findings support the notion that Coa_NP2 exerts its hypotensive action, at least in part, through stimulation selleck screening library of NO production. As such, there are three different receptor isoforms for the NPs, namely, natriuretic peptide receptor A (NPR-A), natriuretic peptide receptor B (NPR-B), and natriuretic peptide receptor C (NPR-C), in which the human NP family have been shown natriuretic, diuretic, hypotensive and vasodilator actions [20] and [22]. It has recently been suggested that BNP exerts its vascular effects through the same pathway as ANP, i.e. the NPR-A. This guanylate cyclase-coupled receptor

is located both on endothelial and vascular smooth muscle cells [37]. Activation of NPR-A generates the second messenger cyclic guanosine monophosphate (cGMP) which, in turns, activates Ca2+ channels and ATP-sensitive K+-channels leading to vasorelaxation [21] and [29]. However, CNP binds to the NPR-B, a specific tetracosactide guanylate cyclase-coupled receptor, and it is located on the vascular smooth muscle cell, also leading to vasodilatation through hyperpolarization [19]. To evaluate the possible mechanisms responsible for these dose-dependent hypotensive effects, we used endothelium-denuded rings preparations (Coa_NP2-e−). It was observed that vasorelaxation produced by the Coa_NP2 in thoracic aortic rings precontracted with phenylephrine was endothelium-dependent, as evidenced by its abolition when it was used Coa_NP2-e−. (Coa_NP2-e+ or Coa_NP2-e− group, respectively, Fig. 5). Similar findings were revealed by other NPs originated from different snake venoms [10] and [38]. The vasorelaxant effect caused by Coa_NP2 seems not to be involved in the NP receptor type A (NPR-A).