The EFFECTS OF CENTRAL ADMINISTRATION OF Ω‐CONOTOXIN GVIA ON CARDIOVASCULAR PARAMETERS AND AUTONOMIC REFLEXES IN CONSCIOUS RABBITS

Abstract

1. The effects of central administration of omega-conotoxin GVIA (omega-CTX), an N-type calcium channel blocker, were examined in conscious rabbits implanted with lateral intracerebroventricular (i.c.v.) cannulae. 2. Experiments were performed over 4 consecutive days. On day 1, the baroreceptor heart rate (induced by glyceryl trinitrate and phenylephrine) and Bezold-Jarisch like (elicited by serotonin) reflexes were measured before (0 h) and 2 h after central administration of omega-CTX (3 or 30 pmol/kg, i.c.v.) or vehicle. On days 2-4, resting parameters and reflexes were again monitored but no further omega-CTX was administered. 3. No change in heart rate (HR) was observed in any rabbit treatment group during the experimental period. In the vehicle (n = 6) and omega-CTX 3 pmol/kg (n = 6) groups, small falls in mean arterial pressure (MAP) of 6 +/- 2 and 10 +/- 3 mmHg, respectively, occurred between 0 and 24 h; MAP then remained stable. Baroreceptor-heart rate reflex curve parameters did not change in either of these groups during the 4 day period. 4. Following administration of omega-CTX 30 pmol/kg (n = 7), MAP decreased progressively and by 48 h had fallen by 19 +/- 4 mmHg. Also at 48 h, a 20% decrease in HR range of the baroreceptor-heart rate reflex curve was seen without any change in the lower HR plateau from the 0 h control. This indicates that there was an attenuation of the sympathetically mediated upper component of the curve while the vagally mediated component was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…When given intravenously, the acute sympatholytic and vagolytic eects of GVIA resolve after 48 h, but a second hypotensive and bradycardic phase lasts a further 96 h . When GVIA is given into the cerebral ventricle the haemodynamic (hypotensive) eects are blunted and have a 48 h delay in onset (Whorlow et al, 1994). Given the theoretical advantages of a faster onset and oset N-channel antagonist for allodynia and neuropathic pain, there is much interest in novel but still selective agents for blocking N-type voltage-operated calcium channels.…”

“…In rabbits, central administration of GVIA requires 48 h to reach a maximum eect following a single i.c.v. bolus of drug (Whorlow et al, 1994).…”

Cardiovascular reflex responses after intrathecal ω‐conotoxins or dexmedetomidine in the rabbit

“…Central (cerebroventricular) injection of GVIA in rabbits also induces hypotension and selective sympatholytic baroreceptor‐HR effects 21 and intracerebroventricular dexmedetomidine attenuates baroreceptor‐mediated vasoconstrictor responses, 9 but these findings cannot be extrapolated to thoracic intrathecal injections.…”

“…Given intravenously, CVID, MVIIA and GVIA all induce postural hypotension and block of the sympathetic and vagal components of the baroreceptor-HR response. 7,8,19,20 Central (cerebroventricular) injection of GVIA in rabbits also induces hypotension and selective sympatholytic baroreceptor-HR effects 21 and intracerebroventricular dexmedetomidine attenuates baroreceptor-mediated vasoconstrictor responses, 9 but these findings cannot be extrapolated to thoracic intrathecal injections.…”

Review: Ca2+ channel sub‐types in peripheral efferent autonomic nerves

“…It is interesting to note that microgram amounts of N channel inhibitors injected i.c.v. in rats tended to initially stimulate and later depress cardiovascular parameters (Shapira, Adeyemo & Feuerstein, 1990;Bowersox et al, 1992), while in rabbits, central administration resulted in a slowly developing sympatholytic but not vagolytic action (Whorlow, Angus & Wright, 1994). The majority of the relevant studies on cardiovascular tissue, both in vitro and in vivo, suggest that the inhibition of N channel activity leads to inhibition of sympathetic function relative to the inhibition of the vagal component (Pruneau & Angus, 1990b).…”