Haemodynamic and humoral effects of omega-conotoxin GVIA in normotensive and spontaneously hypertensive rats.

Omega-conotoxin GVIA, a 27-amino acid peptide, has been shown to be a potent and selective inhibitor of N-type voltage-operated calcium channels (VOCCs). A single intravenous dose of 10 micrograms/kg conotoxin slowly lowered blood pressure by 41.3 +/- 4.4 and 73.3 +/- 4.6 mm Hg in conscious Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) respectively without changing the heart rate. Plasma renin activity was significantly increased after conotoxin. In anaesthetized rats, conotoxin (3 and 10 micrograms/kg) lowered blood pressure and heart rate and produced a marked increase in renal vascular conductances. Baroreceptor heart rate reflex experiments using methoxamine and sodium nitroprusside before and after treatment with conotoxin showed that conotoxin almost totally abolished the sympathetic component of the reflex without affecting the vagal tone to the heart in both rat strains. Because conotoxin does not affect directly the vasculature and heart contractile properties, we suggest that the control of presynaptic calcium influx and of neurotransmitter release mostly depends on conotoxin-sensitive N-type VOCCs in the peripheral sympathetic system of the rat.