Hemodynamic and Autonomic Reflex Effects of Chronic N-Type Ca2+ Channel Blockade with ω-Conotoxin GVIA in Conscious Normotensive and Hypertensive Rabbits

Abstract

The effects of chronic administration of ω-conotoxin GVIA (ω-CTX). an N-type Ca2+ channel blocker, on hemodynamics and autonomic reflexes were studied in conscious normotensive (sham) and hypertensive (wrap) New Zealand white rabbits. During surgery, a pulsed Doppler-flow probe was implanted around the lower abdominal aorta, and both kidneys were wrapped in cellophane (wrap) or left undisturbed (sham). Rabbits were studied 4 weeks later on 5 consecutive days. On days 1–4, hemodynamics, the baroreceptor-heart-rate (HR) reflex induced by drugs and the Bezold-Jarisch-like reflex evoked by serotonin, were measured before and 2 h after administration of ω-CTX (10 μg/kg i.v. bolus). On day 5, hemodynamics and reflexes were again assessed, but no further ω-CTX was given. On day I, ω-CTX caused falls in mean arterial pressure (MAP) of 17 ± 3 and 27 ± 5 mm Hg in sham (n = 6) and wrap (n = 11) rabbits, respectively, with tachycardia. Hindquarter vascular conductance (HVC) increased >35% in both groups. On days 2–4,ω-CTX still caused falls in MAP; however it was progressively less than on day I. HR and HVC did not change. After ω-CTX on day I, there was marked attenuation of the sympathetic components and decrease in the vagal components of the baroreceptor-HR reflex curves, with HR range decreasing by >61% in sham and wrap rabbits. These curves remained similar over the next 4 days, and were unaffected by further ω-CTX. However. ω-CTX had no effect on the vagally mediated Bczold-Jarisch-like reflex. In auxiliary experiments in vitro, ω-CTX (1 nM) inhibited sympathetic, but not vagal, responses to electrical nerve stimulation of rabbit-isolated right atria. Thus, ω-CTX is a potent hypotensive agent in normotensive and hypertensive rabbits, predominantly via a peripheral sympatholytic action with no effect on vagal-cardiac efferent activity. However, it may affect the vagal component of the baroreceptor-HR reflex by an unknown central mechanism.