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

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Abstract
The effects of a novel N‐type voltage‐operated calcium channel antagonist, ω‐conotoxin CVID, were compared with ω‐conotoxin MVIIA on sympathetic‐evoked activation of right atria (RA), small mesenteric arteries (MA) and vasa deferentia (VD) isolated from the rat. Their effects were also compared on blood pressure and cardiovascular reflexes in conscious rabbits. The pIC50 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 offset rates for CVID and MVIIA were rapid, and peptide reapplication caused rapid onset of blockade, suggesting limited desensitization. In the conscious rabbit, CVID and MVIIA (100 μg kg−1 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 baroreflex, but had no effect on the vagal nasopharyngeal reflex. The orthostatic reflex to 90° tilt was blocked by MVIIA with sustained postural hypotension for 90 min after administration. In contrast, CVID caused postural hypotension at 30 min which recovered rapidly. Neither CVID nor MVIIA (3 μg kg−1 i.t.) significantly altered cardiovascular variables or autonomic reflexes. In conclusion, CVID appears to be relatively weak at inhibiting the reflex 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. British Journal of Pharmacology (2000) 131, 1325–1336; doi:10.1038/sj.bjp.0703701