Endogenous angiotensin II and bradykinin delay and attenuate the hypotension after N-type calcium channel blockade in conscious rabbits

The effects of N-type calcium channel inhibition with omega-conotoxin GVIA (omega-CTX) on cardiovascular parameters and vagally mediated autonomic ref lexes and the role of the renin-angiotensin system were assessed in conscio us rabbits. omega-CTX (10 mu g/kg, i.v.) resulted in hypotension, tachycard ia, and attenuation of the sympathetic and vagal components of the barorece ptor-heart rate reflex (baroreflex). In the control group (no pretreatment) , the peak decrease in mean arterial pressure (MAP) of 13 +/- 3 mm Hg from 72 +/- 2 mm Hg occurred after 33 +/- 3 min, with a corresponding tachycardi a of 80 +/- 20 beats/min (n = 6). The tachycardia was due to vagal withdraw al, as a similar increase in heart rate (84 +/- 8 beats/min) after omega-CT X was observed after pretreatment with the beta-adrenoceptor antagonist, pr opranolol (n = 6). Angiotensin-converting enzyme (ACE) inhibition with enal aprilat revealed a larger, more rapid decrease in MAP in response to omega- CTX (-19 +/- 4 mm Hg from 65 +/- 1 mm Hg after 18 +/- 2 min; n = 6) compare d with the control group. Similar larger decreases in MAP were also observe d in the presence of the AT(1)-receptor antagonist, losartan, or the bradyk inin B-2 receptor antagonist, HOE-140 (n = 5-6). Pretreatment with enalapri lat, losartan, or HOE-140 caused a 50% decrease in the reflex tachycardia a fter omega-CTX compared with that observed in the control group, and omega- CTX caused a greater attenuation of the vagal component of the baroreflex a nd a decrease in the bradycardia evoked by the Bezold-Jarisch-like reflex. Also, there was a significant decrease in the bradycardia induced by the na sopharyngeal reflex after omega-CTX in the presence of ACE inhibition and H OE-140. Thus in the conscious rabbit, angiotensin II and bradykinin have a role in attenuating and slowing the hypotensive effect of N-type calcium ch annel inhibition. Vagolytic effects of omega-CTX on the baroreflex are augm ented, and on other vagal reflexes are unmasked, via inhibition of the reni n-angiotensin system. The complexity and mechanism of the interaction betwe en N-type calcium channels and the renin-angiotensin system remain to be el ucidated.