(Hypertension. 2001;37:1268.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Comparative Effects of Selective T- and L-Type Calcium Channel Blockers in the Remnant Kidney Model
From the Departments of Medicine (K.A.G., A.K.B.) and Pathology (M.P.), Loyola University Medical Center and Hines Veterans Administration Hospital, Maywood; and Department of Preventative Medicine, Rush-Presbyterian St. Luke’s Medical Center (G.L.B.), Chicago, Ill.
Correspondence to Karen A. Griffin, MD, Loyola University Medical Center, Section of Nephrology, 2160 S First Ave, Maywood, IL 60153.
Abstract—We
have previously reported that the dihydropyridine
L-type calcium channel blockers (CCBs) have an adverse impact on
glomerulosclerosis (GS) in the remnant kidney
model despite significant blood pressure (BP) reduction, because of the
concurrent deleterious effects on renal autoregulation. The effects of
the CCB mibefradil, which is 
10-fold more selective for T- than
L-type channels, were compared with the L-type selective amlodipine.
One week after 5/6 ablation, rats were left untreated or received
mibefradil or amlodipine. Systolic BP was monitored by
continuous radiotelemetry. At 7 weeks, proteinuria and percent GS were
quantitated. Average BP was significantly and comparably reduced after
mibefradil (141±3 mm Hg) and amlodipine (143±5 mm Hg)
compared with untreated rats (188±5 mm Hg). Despite the
reduction in BP, proteinuria and percent GS in the mibefradil- or
amlodipine-treated groups were not significantly different from those
in the untreated rats. Excellent correlations were observed between BP
and GS in each group (r=0.74 to
0.85, P<0.02). However, the
slope of the relationship between GS and BP (increase in percent
GS/mm Hg increase in average BP) was made significantly steeper by
both mibefradil (2.7+0.6) and amlodipine (1.9+0.6) as compared with
untreated rats (0.7±0.2;
P<0.01). Thus, at any given BP
elevation, greater GS was seen in mibefradil- and amlodipine-treated
rats as compared with untreated rats. Additional studies performed at 3
weeks after renal ablation showed that the ability to autoregulate
renal blood flow, already impaired in untreated rats, was essentially
abolished by both mibefradil and amlodipine, thus providing an
explanation for the shift in the slope of the relationship between BP
and GS. These data indicate that CCBs with selectivity for either the
T- or L-type calcium channel fail to protect against GS despite
significant BP reductions because of the similar adverse effects on
renal autoregulation and BP transmission.
Key Words: glomerulosclerosis • nephrectomy • hypertension, experimental • telemetry • blood pressure • autoregulation
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