BJ-PRO-7A and BJ-PRO-10C induce vasodilatation and inotropic effects in normotensive and hypertensive rats: Role of nitric oxide and muscarinic receptors

Structural Characterization and Rat Aortic Vascular Reactivity of Bradykinin-Potentiating Peptides (BPPs) from the Snake Venom of Bothrops moojeni from Delta do Parnaíba Region, Brazil

“…4 Besides, Bj-PRO-7a and Bj-PRO-10c were also able to induce a vasorelaxant effect possibly involving the NO/sGC/cGMP pathway and AsS activity. 30 In the present study, the vasorelaxant effects of BPP-Bm01, BPP-Bax12, and BPP-13a in rat aortic preparations were reported. The peptides induced a significant concentration-dependent vasorelaxant effect with the maximal effects thereof observed at 37.5%, 32.8%, and 18.3% for BPP-Bm01, BPP-Bax12, and BPP-13a, respectively, in endothelium-functional rat thoracic aorta preparations (Figure 5A, B, and C, respectively).…”

“…Arcanjo and collaborators reported the vasorelaxant effects of BPP-BrachyNH 2 at the same intensity as captopril and the involvement of nitric oxide in this response . Besides, Bj-PRO-7a and Bj-PRO-10c were also able to induce a vasorelaxant effect possibly involving the NO/sGC/cGMP pathway and AsS activity . In the present study, the vasorelaxant effects of BPP-Bm01, BPP-Bax12, and BPP-13a in rat aortic preparations were reported.…”

“…The involvement of proline-rich oligopeptides (PROs) in increasing NO production has been attributed to the activation of the enzyme AsS. , In a previous study, the Bj -BPP-10c identified in B. jararaca venom was internalized in endothelial cells and increased the enzymatic activity of AsS, resulting in the conversion of l -citrulline into l -arginine and promoting an increase in intracellular and plasma levels of l -arginine, with consequent formation of NO. , Moreover, the peptide Bj -BPP-10c-induced vasorelaxant and antihypertensive effects were abolished in the presence of α-methyl- d , l -aspartic acid (MDLA), an inhibitor of AsS, in spontaneously hypertensive rat (SHR) but not in normotensive rats. Therefore, as physiological intracellular levels of l -arginine are sufficient to saturate substrate binding to endothelial nitric oxide synthase (eNOS), AsS might be considered as a putative target for recycling l -arginine to restore endothelial NO production and promote vasorelaxant response only when NO production is pathologically altered.…”

Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (<EDGPIPP) from Bothrops jararaca snake venom rescues oxidative stress-induced neurotoxicity in PC12 cells

“…Studies have revealed that PRO-7a is an M1 mAChR agonist, which is of critical relevance given the extensive research that focused on finding such a ligand [ 24 , 57 , 58 ]. The peptide specifically activates [Ca 2+ ] I transients in CHO and neuronal P19 cells expressing the M1 mAChR subtype, which are inhibited in cells pretreated with the M1 mAChR specific antagonist pirenzepine [ 24 ].…”

Cardioprotective effects of the proline‐rich oligopeptide Bj‐PRO‐7a in spontaneously hypertensive rats

“…In this sense, several studies have shown significant biological activities of peptides extracted from snake venom in the cardiovascular system. [5][6][7][8] A remarkable advancement in the treatment of hypertension was the development of captopril, the first angiotensinconverting enzyme (ACE) inhibitor. Captopril was developed based on the structure of a bradykinin-potentiating peptide isolated from the venom of the Brazilian snake Bothrops jararaca (Bj).…”