It is estimated that there are about 170,000 venomous species throughout the world. The venom produced by their glands contains hundreds of bioactive compounds. These natural libraries open complete new therapeutic avenues. Heart failure is a cardiac disease associated with morbidities. Recent progress in medicine allowed to develop treatments, yet they are often not highly efficient and possess harmful side effects. Given that venom compounds are pharmacologically active, they can be considered as a source of life-saving therapeutics.

The aim of our study is to find therapeutic effects of venom compounds to treat hypertension which can lead to heart failure.

Black Mamba snake venom fractionations were performed by using cation exchange and RP-HPLC techniques. The obtained fractions and purified compounds were investigated for their ability to displace ³H-NMS from muscarinic type 2 receptors (M2R). One particular snake peptide, found to be active, was de novo sequenced and synthesized. This peptide was studied in vivo by invasive hemodynamics to evaluate the main cardiovascular parameters (n=5, 100μg/kg) and ex vivo on isolated mesenteric and aorta arteries (n=6; 0.8nM, 8nM, 80nM and 8μM). Wistar rats that were 10–12 weeks old were used for this study.

After consecutive fractionations of the venom, we succeeded to identify a unique peptide with major hypotension effects. Once injected intravenously in vivo, invasive hemodynamic studies highlighted a significant arterial blood pressure decrease (−65%, P<0.001) and a reduction in heart rate (−14%, P<0.001). It also induced a relaxation of mesenteric and aorta arteries (−90%, P<0.05 vs. baseline). Whether these effects are due to M2R, their regulation will be discussed.

In this study, we demonstrated the hypotensive effect of an isolated peptide from Black Mamba snake. These results confirm that venom compounds represent a promising opportunity to develop new drugs.