Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Abstract

1 The eects of a novel N-type voltage-operated calcium channel antagonist, o-conotoxin CVID, were compared with o-conotoxin MVIIA on sympathetic-evoked activation of right atria (RA), small mesenteric arteries (MA) and vasa deferentia (VD) isolated from the rat. Their eects were also compared on blood pressure and cardiovascular re¯exes in conscious rabbits. 2 The pIC 50 values for MVIIA and CVID, respectively, for inhibiting sympathetic-evoked responses were equivalent in RA (8.7 and 8.7) and VD (9.0 and 8.7); however, in MA the values were 8.4 and 7.7. The cardiac to vascular (RA/MA) potency ratios, antilog (plog RA ± plog MA), for MVIIA and CVID were 2 and 10. The oset rates for CVID and MVIIA were rapid, and peptide reapplication caused rapid onset of blockade, suggesting limited desensitization. 3 In the conscious rabbit, CVID and MVIIA (100 mg kg 71 i.v.) caused a similar fall in blood pressure and a tachycardia that rapidly reached maximum. Both peptides decreased the vagal-and sympathetic-mediated components of the barore¯ex, but had no eect on the vagal nasopharyngeal re¯ex. The orthostatic re¯ex to 908 tilt was blocked by MVIIA with sustained postural hypotension for 590 min after administration. In contrast, CVID caused postural hypotension at 30 min which recovered rapidly. 4 Neither CVID nor MVIIA (3 mg kg 71 i.t.) signi®cantly altered cardiovascular variables or autonomic re¯exes. 5 In conclusion, CVID appears to be relatively weak at inhibiting the re¯ex response to tilt consistent with its weaker inhibition of rat mesenteric artery constriction to perivascular nerve stimulation. This may point to subtype N-type calcium channel selectivity.

Analgesic Effect of Highly Reversible ω-Conotoxin FVIA on N Type Ca2+ Channels

“…When a relatively low CTx dose (10 μg/kg) was intravenously administered into rats, in fact, we could not observe any apparent difference between CTx-FVIA and CTx-MVIIA in recovery pattern of blood pressure. Similarly it was reported that Wright et al used a high dose of toxin (100 μg/kg) in an experiment for cardiovascular and autonomic effects [60]. As with its effect on N-type Ca 2+ currents, the effect of CTx-FVIA on blood pressure was more reversible than that of CTx-MVIIA (Figure 2C and Figure 6).…”

Analgesic ω-Conotoxins CVIE and CVIF Selectively and Voltage-Dependently Block Recombinant and Native N-Type Calcium Channels

“…On the other hand, the block by -conotoxin CVIB, an antagonist of both N-and P/Q-type VGCCs, has been shown recently to reversibly inhibit excitatory synaptic transmission in the spinal cord (Motin and Adams, 2008). Recovery from block may influence how effectively -conotoxins reverse different painful conditions in vivo, and could indicate whether administration of these peptides can be controlled to avoid unwanted side effects (Wright et al, 2000).…”

Cardiac Tissue Engineering in an In Vivo Vascularized Chamber

“…A transverse section of tissue 1 to 2 mm thick was cut from the construct, placed immediately in physiological salt solution 26 at 37°C, and saturated with 95% O 2 and 5% CO 2 during the experiment. The tissue was mounted vertically between stainless steel S-shaped hooks on an acrylic leg in physiological salt solution-filled 20-mL glass-jacketed organ bath heated to 37°C.…”