Hemodynamic and autonomic reflex effects of chronic N-type Ca2+ channel blockade with omega-conotoxin GVIA in conscious normotensive and hypertensive rabbits.
The effects of chronic administration of omega-conotoxin GVIA (omega-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 omega-CTX (10 micrograms/kg i.v. bolus). On day 5, hemodynamics and reflexes were again assessed, but no further omega-CTX was given. On day 1, omega-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, omega-CTX still caused falls in MAP; however it was progressively less than on day 1. HR and HVC did not change. After omega-CTX on day 1, 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 omega-CTX. However, omega-CTX had no effect on the vagally mediated Bezold-Jarisch-like reflex. In auxiliary experiments in vitro, omega-CTX (1 nM) inhibited sympathetic, but not vagal, responses to electrical nerve stimulation of rabbit-isolated right atria. Thus, omega-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.
Wright
C E
CE
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Angus
J A
JA
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D012018:Reflex / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010455:Peptides; D020866:omega-Conotoxin GVIA