1. Trans-
diclofurime has been shown to be a potent group II
calcium antagonist in in vitro and in vivo test systems. In contrast to the
dihydropyridines, group II
calcium antagonists have a reduced propensity to cause reflex
tachycardia due to well-balanced inhibitory effects in smooth muscle and heart. Since effects on autonomic reflexes are more reliably assessed in conscious animals, the cardiovascular effects of trans-
diclofurime have been examined and compared to those of
nifedipine,
verapamil and
diltiazem in the conscious spontaneously hypertensive rat (SHR). 2. Each SHR had an
indwelling catheter in the femoral artery to record mean arterial pressure (MAP) and heart rate (HR) and a
cannula in the femoral vein for
drug infusion over 1 min. 3.
Nifedipine (0.1-3.0 mumol kg-1 i.v.) caused dose-related falls in MAP accompanied by dose-related increases in HR. Trans-
diclofurime and
verapamil (0.3-3.0 mumol kg-1 i.v.) also caused dose-related decreases in MAP, but significant
tachycardia was only seen at 1.0 and 3.0 mumol kg-1. Trans-
diclofurime (0.3 mumol kg-1) induced a significant fall in HR.
Diltiazem (1.0-10.0 mumol kg-1 i.v.) induced dose-related falls in MAP, significant
bradycardia was evident with 1.0 mumol kg-1 and
tachycardia with 10 mumol kg-1. Trans-
diclofurime and
diltiazem induced less
tachycardia than
nifedipine and
verapamil for equivalent falls in MAP. 4. These results suggest that trans-
diclofurime is a potent
antihypertensive agent in conscious SHR and, like
diltiazem, the hypotensive effects are associated with less
tachycardia than is usually apparent with
calcium antagonists such as
nifedipine or
verapamil. S. The cardiovascular effects of trans-
diclofurime in conscious SHR are those expected of a class II
calcium antagonist and are consistent with its proposed mode of interaction with the
diltiazem site in the
calcium channel.