DIFFERENTIAL EFFECTS OF T- & L-TYPE CALCIUM CHANNEL BLOCKADE ON
AUTONOMIC FUNCTION IN PATIENTS WITH MILD-MODERATE ESSENTIAL HYPERTENSION A-M. Pellizzer1*,
P.W. Kamen1, M. Esler2, S. Lim1 and H. Krum1 1Clinical
Pharmacology Unit, DEPM, Monash University, Alfred Hospital, 2Baker
Medical Research Institute, Prahran VIC. Conventional L-type
dihydropyridine CCBs have been implicated in cardiovascular
events in pts with hypertension, perhaps due to adverse effects on autonomic
nervous system (ANS) function. It has been proposed that selective blockade of
T-type calcium channels may limit ANS dysfunction due to inhibition of T
channel-mediated neuroendocrine effects. To test this, we performed a
double-blind, parallel group study comparing the effect of nifedipine GITS (N,
L-type CCB) vs mibefradil (M, T-type CCB) on ANS function in pts with
mild-moderate essential hypertension. Sixteen patients (10M, 6F;
age 57+10 yrs) with DBP >95 mmHg were randomised (1:1 ratio) to N 30
mg daily or M 50 mg daily for 2 wks, then N 60 mg daily or M 100 mg daily for a
further 4 wks. Sympathetic activity (SNSA)
was assessed by circulating levels of noradrenaline (NA) and 3[H]NA
spillover rate. Parasympathetic activity (PSNA) was assessed from 24-hr Holter
of heart rate variability (HRV) including rMSSD and high frequency power
[HFP]). HFP was also normalised for total power (TP) to account for changes in
HR. Integrated assessment of ANS was determined from non-invasive baroreflex
sensitivity (BRS). Pts in both groups were well
matched at baseline. Wk 0 vs wk 6 differences for each group are summarised in
the Table. Achieved DBP was lower in pts treated with M cf N. There were no
significant differences in SNSA and BRS between groups, however rMSSD and HFP
were in M- cf N-treated pts. Furthermore, LnHF/LnTP was
from
Wk 0 to Wk 6 in the M-treated group. DHR DDBP D
DNA
DBRS DrMSSD DLnHFP D
Ln bpm mm
Hg pg/ml ng/min ms/
mmHg ms ms2 N +3.1+2.3 -9.0+2.7 +99.4 +193.6 -1.43+1.3 -3.4+1.2+ -0.23+0.1 -0.00+0.02 M -3.0+3.3 -17.3+1.7 +113.7 +253.4 -0.62+1.3 +1.+1.6 +0.28+0.1+ +0.03+.01+ P 0.16 0.03 0.85 0.58 0.68 0.05 0.01 0.21 *P value for M vs N; +P<0.05
for wk 0 vs Wk 6; #NA results expressed as differences in median
values It is concluded that no differences exist between effect of L- type and
T-type CCBs on SNSA and BRS. However, T-type CCBs appear to
PNSA,
independent of achieved changes in heart rate.
Plasma NA#
Spill-
over#
HFP/
LnTP
