Acute Effects Of L- And T-Type Calcium Channel Antagonists On Cardiovascular Reflexes In Conscious Rabbits

SUMMARY 1. The effects of the relatively selective T‐type voltage‐ operated calcium channel (VOCC) antagonist mibefradil were compared with verapamil, an L‐type VOCC antagonist, on a range of autonomic reflexes in conscious rabbits. 2. Mean arterial pressure (MAP), heart rate (HR), the baroreceptor–HR reflex, postural adaptation reflex (90° head‐up tilt), Bezold–Jarisch‐like reflex and the vasoconstrictor component of the nasopharyngeal reflex were assessed before and during i.v. infusion of vehicle (saline), mibefradil or verapamil. Doses of mibefradil that gave low (M1; 0.45 ± 0.02 μg/mL) and high (M2; 0.93 ± 0.05 μg/mL) plasma concentrations, or verapamil (0.059 ± 0.004 μg/mL; n = 6 each) were chosen to mimic clinically observed therapeutic levels. 3. At steady state infusion over 30–90 min, MAP was significantly lower in M2 (– 7 mmHg) and verapamil (– 6 mmHg) treatments, but only verapamil caused a significant tachycardia (+ 31 b.p.m.) compared with vehicle. Mibefradil (M2) and verapamil decreased the HR range of the baroreflex by 27 and 29%, respectively, but neither treatment affected the vagal or sympathetic constrictor components of the Bezold–Jarisch‐like and nasopharyngeal reflexes, respectively. 4. In response to 90° tilt, vehicle‐ and verapamil‐treated rabbits responded with small rises in MAP of 4 ± 2 and 8 ± 2 mmHg, respectively, 5 s into the upright posture, while M1 and M2 caused falls in MAP of 6 ± 4 and 9 ± 3 mmHg, respectively, at 5 s. 5. Thus, both L‐ and T‐type VOCC antagonists, at plasma concentrations in the clinical range, lowered MAP in the conscious rabbit, but only mibefradil caused postural hypotension. We conclude that T‐type VOCC may play an important role in the venoconstrictor reflex in response to tilt in the rabbit.