Vampire Venom: Vasodilatory Mechanisms of Vampire Bat (Desmodus rotundus) Blood Feeding

Abstract

Animals that specialise in blood feeding have particular challenges in obtaining their meal, whereby they impair blood hemostasis by promoting anticoagulation and vasodilation in order to facilitate feeding. These convergent selection pressures have been studied in a number of lineages, ranging from fleas to leeches. However, the vampire bat (Desmondus rotundus) is unstudied in regards to potential vasodilatory mechanisms of their feeding secretions (which are a type of venom). This is despite the intense investigations of their anticoagulant properties which have demonstrated that D. rotundus venom contains strong anticoagulant and proteolytic activities which delay the formation of blood clots and interfere with the blood coagulation cascade. In this study, we identified and tested a compound from D. rotundus venom that is similar in size and amino acid sequence to human calcitonin gene-related peptide (CGRP) which has potent vasodilatory properties. We found that the vampire bat-derived form of CGRP (i.e., vCGRP) selectively caused endothelium-independent relaxation of pre-contracted rat small mesenteric arteries. The vasorelaxant efficacy and potency of vCGRP were similar to that of CGRP, in activating CGRP receptors and Kv channels to relax arteriole smooth muscle, which would facilitate blood meal feeding by promoting continual blood flow. Our results provide, for the first time, a detailed investigation into the identification and function of a vasodilatory peptide found in D. rotundus venom, which provides a basis in understanding the convergent pathways and selectivity of hematophagous venoms. These unique peptides also show excellent drug design and development potential, thus highlighting the social and economic value of venomous animals.

Keywords: Desmodus rotundus; calcitonin gene-related peptide; potassium channels; vampire bat; vasodilatation; venom.

Figure 1

Alignments of vCGRP (Vampire bat), rCGRP (Rat), and hCGRP (human) with cysteines shaded in black and vampire bat specific modified residues in green.

Figure 2

D. rotundus vCGRP causes vasodilation similar to rCGRP via CGRP1 receptors. Cumulative concentration-response curves to (A) D. rotundus vCGRP (n = 23) and rat CGRP (n = 23) alone and (B) D. rotundus vCGRP (n = 10) and (C) rat CGRP (n = 7) in the absence and presence of CGRP8-37 (100 nM, n = 7–10) in rat small mesenteric arteries. Values are expressed as % reversal of pre-contraction and given as mean ± SEM, where n = number of animals. * p < 0.05 pEC50 versus control, student’s unpaired t-test.

Figure 3

The soluble guanylyl cyclase or adenylyl cyclase pathways do not play a role in vasorelaxation induced by D. rotundus vCGRP or rCGRP. Cumulative concentration-response curves to D. rotundus vCGRP (A–C) or rat CGRP (D–F) in rat small mesenteric arteries in the absence (D. rotundus vCGRP, n = 6–12; rat CGRP, n = 5−9) or presence of either L-NAME (100 µM, n = 9–10), ODQ (10 µM, n = 5–7), SQ22536 (10 µM, n = 6) or following endothelial denudation (n = 7). Values are expressed as % reversal of pre-contraction and given as mean ± SEM, where n = number of animals. * p < 0.05 pEC50 versus control, student’s unpaired t-test.

Figure 4

Voltage-gated potassium channels significantly attenuate the vasodilatory effects of D. rotundus vCGRP and rCGRP. Cumulative concentration-response curves to (A) D. rotundus vCGRP (n = 17) or (B) rat CGRP (n = 12) in rat small mesenteric arteries from rats in the absence or presence of either 30 mM K⁺ (n = 7–9), TEA (1 mM, n = 6−8), glibenclamide (10 µM, n = 6) or 4-aminopyridine (1 mM, n = 6–8). Values are expressed as % reversal of pre-contraction and given as mean ± SEM, where n = number of animals. * p < 0.05, concentration-response curve significantly different as compared to control (2-Way ANOVA). # p < 0.05, response at 30 nM or 10 nM significantly different as compared to control (1-Way ANOVA, Bonferroni’s post hoc).