46
Medical Research Society
P
170
RENAL EUNCTION IN NISXDIPINE TREATED -ION
J. WIISCRI, M. WAHBAH, R HRINSWRl7-I. J A DAVIES
C.R.M. PRFIWICE
AM)
Univ. Dept. of Medicine, General Infirmary, Leeds.IS1 W
Nisoldipine is a 1,4 dihydromnidine calcium antagonist
with vasodilator properties. Acute administration to
humans causes an increase in glomerular filtration rate
(GFR) and effective renal plasma flow (EWF (11, but
longer term effects on renal function are unknown. We
have investigated in a placebo controlled double blind
cross-over study the effect of nisoldipine treatment of
moderate hypertension on renal function. 13 hypertensive
subjects were studied and all previous therapy was
withdrawn prior to entry. Supine and standing blood
pressure (BP) and heart rate (HR) were measured on four
occasions: on admission (A), after 4 weeks on placebo
(B), and after 6 and 12 weeks of the cross-over phase
with either nisoldipine (C) or placebo (D). WR, ERPF,
cardiac output (a),
serum biochemistry and haematolcgy
were measured at times (B), (C) and (D), and plasma renin
activity (PRA) was measured at tims (C) and (D).
Nisoldipine was effective in lowering both supine and
standing BP respectively (A) 160/103, 156/107, (B)
154/102, 155/106, (C) 143/90, 139/96, (D) 155/100,
150/105, (p < Om), whereas supine and standing HR were
unchanged. GFR was not significantly aff-ed
by
nisoldipine [(B) 91, (C) 85, (D)90 ml min- 1.73-2 and
neithy was ERPF [(B) 375, (C) 341, (D) 359 ml min-'
1.73- 1 or CO [(B) 3.4, (C) 3.2 (D) 3.3 1 min-' 1.73-21.
Haematolcgy and s e r u m biochemistry remained unaltered,
and PRA was not significantly affected
trea ment with
nisoldipine [ ( C ) 1.18, (D) 0.84 pmol
' d m
i
n
'
I
.
In this group of patients, nisoldipine was an effective
antihypertensive agent and had IY) untoward effect on
renal function.
PA. Meredith. Br. J. clin. Pharmac. (1985), 20, 235237.
171
DETECTION OF RENAL ARTERY STENOSIS (RAS) WITH
CAPTOPRIL ENHANCED 99m-Tc DTPA SCINTIGRAPHY
E.R.
AND
MAHER, S. OTHMAN, A.H.
A.J.W. HILSON
FRANKEL, P. SWENY
captopril scan. A positive captopril scan had
a sensitivity of 100% and a specificity of
60% in the detection of unilateral RAS. These
results suggest that captopril enhanced 99mTc DTPA scintigraphy may be a useful
screening test for RAS.
DIFFERENTIAL EFFECT OF INFLAMMATORY
MEDIATORS ON MICROVASCULAR PERMEABILITY IN
DIFFERENT PARTS OF THE GUINEA PIGAIRWAYS
172
TW EVANS, DF ROGERS, B AURSUDKIJ.
AND PJ BARNES
Dept. Clinical Pharmacology, Cardiothoracic Institute.
Brompton Hospital, Fulham Road, LONDON SW3 6HP
Asthmatic airways are characterised by oedema d plasma
exudation resulting from increased microvascular leakage.
Several imflammatory mediators may contribute t o these
chages. We have shown previously t h a t platelet activating
factor (PAF) increases microvascular leakage in guinea pig
airways, most potently in main bronchi (J. Appl. Physiol..
63(2). in press). In t h e present study, we investigated
t h e role and distribution o f effect o f PAF, histamine and
leukotriene ( L T ) D4 in increasing vascular permeability in
guinea pig airways. Microvascular permeability was assessed
by extravasation o f Evans blue (EB) d y e which binds t o
albumin. A f t e r anaesthesia, EB d y e was given iv and l m i n
later PAF (50nglkg. n=6). histamine (150pg/kg. n=6) o r
LTD (50ng/kg. n=7). Control animals (1-141 received l m l
sali&. A f t e r 5min animals were perfused with paraformaldehyde and t h e trachea, main bronchi and central and
peripheral intrapulmonary airways removed. EB d y e was
extracted in formamide and quantified by spectrophotanetry.
Values are expressed as means f SD. "~(0.05 compared
with controls:
Controls
PAF
Histamine
LTD
Trachea 27.1 (12.2) 112.9 (18.5)" 63.5 (15.5)* 59.7 (18.8)*
Main br. 32.8 (14.6) 134.5 (48.3)* 61.4 (15.1)* 74.6 (20.4)*
Central 46.3t14.5) 101.5 (20.1)* 51.7 (38.2) 80.7 (16.1)*
Periph. 51.1 (25.7) 87.6 (29.l)* 34.1 (16.5) 77.3 (24.4)
Although all three mediators signifcantly increased leain a t least two parts o f t h e airway, t h e effect o f PAF was
greatest in main bronchi and decreased peripherally,
histamine increased leakage only in t h e trachea and main
bronchi, whilst LTD4 caused a similar increase a t all
airway levels.
We conclude t h a t different inflammatory mediators may
increase microvascular leakage in different parts o f t h e
airway and, if released i n t o t h e airway in man. may
contribute t o t h e inflammation seen in asthmatics.
Departments of Nephrology
and Nuclear
Medicine, Royal Free Hospital, London NW3.
Renal perfusion pressure is reduced in RAS
and GFR is maintained by angiotensin I1
induced
constriction
of
the efferent
arteriole. ACE inhibitors such as captopril
interfere with renal autoregulation and may
produce a reversible reduction in GFR and
filtration fraction in the stenotic kidney.
We have investigated whether captopril
induced changes in split renal function can
be used to screen for RAS. We studied 36
hypertensive patients attending a general
Nephrology clinic with severe hypertension,
asymmetrical kidneys, unexplained renal
failure or systemic vascular disease.
Differential renal function was measured by
99m-Tc DTPA scintigraphy before and one hour
after 25 m g captopril. At arteriography 9
patients had unilateral RAS, 2 had bilateral
RAS and 26 had no RAS. In patients with
unilateral
RAS
the
stenotic
kidney
contributed a mean (SD) of 54 (21) % of total
renal function on the control scan and 44
(18) % on the post captopril scan (p<0.005).
A positive captopril scan, defined as a 5% or
more reduction in the the contribution of the
stenotic kidney to total renal function, was
found in all patients with unilateral RAS.
Six of 26 patients with no RAS had a positive
KF CHUNG
173
-IM
-.
BVT NDT S&WE!MX
LEaKAGE IN aTINFA PIGS.
P. KSaElTQ, N.
BARNES.
M.
T(DBERTs,
D.
INHIBITS AIRWAY
F.-AM)P.J.
Department of C l i n i c a l Pharmacology, Cardiotbracic
Institute, l 3 m n p t m Hcspital, Lcndcll sw3.
Airway oedema may be an important feature of a&ma but
the mechanisms r e g u l a t i n g brcnchia~ mi-iar
leakage a m largely unbzwn. Beta-adrenoceptor agmists
have been repeated to prevent m-iar
leakage
(Persson Ora: L a n c e t 1986;ii:1126). We have studied the
effect of intraveryxls (iv) salbutan~~i(SAL) and
adrenaline (ADR) (at dases of 20, 80 and 16oug/kg) on
airway micrwascular leakage induced by platelet
activatbq factor (PAF: 5ong/kg,iv), which we have
prwiously shewn to be a potent stiniulus of leakage that
a d s directly an endothelial calls (Evans et al, J pppl
Physiol 1987:63(2) in press). MicroMscular permeability
was measured bydeixrmimq
'
exbcavasation of Evans B l u e
aye (3Wg/kg,iv) given 5 min after the
sympattxmh€?tics in aMesthetised guinea pigs. E B w a s
injected, followed 1 min later by PAF, and 5 m i n later
by perfusion of the qst&c circulatian w i t h saline to
rerrwe remaining i n t r m 1 a r dye. The trachea, main
b?xmhi and intraplbmmry airways were r%lwved, EB