Drugs 25 (Suppl. 2): 103-107 (1983)
ooi 2-6667leyo3oo-oro31$02.50/0
O ADlS Press Australasia Pty Ltd (Inc. NSW).
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P-Adrenoceptor Blocking Drugs and Renal Blood
Flow with Special Reference to the Elderly
K. O'Malley, W.G. OICallaghan, M.S. Laher, K. McGarry and
E. O'Brien
The Blood Pressure Cllnlc, The Charitable Infirmary. Jervls Street. Dublln and
Department of Cllnlcal Pharmacology, Royal College of Surgeons In Ireland,
St Stephen's Green, Dublln
Srttritrrary
Adrenergic receptors in the kidney nrediate changes in renal bloodjlow. ~Adrenoceptor
stitnrtlation results in vaoconstriction tvhile stinirtlation of fl,-adrerroceptors h a a similar
effect tnediated through the renin-angiotensin systenr. On the other hand, flTadrenoceptors
niediate direct vasodilatation. Therefore adrenoceptor blockade rnay be expected lo. alter
renal blood /low.
In general. in young patients, cardioselective drugs lend to reduce renal bloodjlow. However, little data are available on the effects ojflblockade in elderly patients. As hypertension
in this grorcp diflers in nrany respects fiorn that in young patients. we observed the antihypertensiveand renal e f i s o/atenolol, nadolol and labetalol hi elderly hypertensive patients.
Oitr data srrggest that in tlre elder1.v. 8-blocking drugs are effectiveantihypertensive agents
but they hare disparate effects on renal bloodjlotv. Cardioselective agents appear to Irat.e
less tendency to redrtce renal bloodjlow than nun-selective ones. Ilowwer, the clinical signi/icance o/sitcli changes in renal bloodjlow in tlre presence of unaltered glonrerularf~ltration rate and nortnal biochen~icalindices ofrenalfinction renrains to be elucidated.
of drugs in this group may be more important than
in younger patients. In this paper we consider the
@-Blockingdrugs have an establislied role in tlie role of adrenoceptors in control of renal blood flow,
treatment of hypertension in young and middle- review existing data on the effect of 8-blockade on
aged patients (Simpson, 1974). Many adversely af- renal function and outline our studies with atenfect glomerular filtration and renal blood flow but 0101, nadolol and labetalol in elderly liypertensive
the clinical significance of such changes is debat- patients.
able (Wilkinson, 1982). The eficacy of &blocking
drugs in lowering blood pressure in elderly patients
with hypertension has not been assessed nor in2. Adrerrergic Receptors and
deed lias their effect on renal blood flow. The elRer~alBlood Flow
derly comprise alrnost half the patients undergoing
treatment for hypertension in the United Kingdom
(Tudor Hart, 1980). Many of these patients have
reduced renal function associated with ageing. In
a-Adrenoceptors are present in the renal vasaddition they are at risk from the effects of hypertension on the kidney; thus, any deleterious effect culalure (Rector et al., 1972) and mediate renal
,
~l.Olockarsarid
llcrlal Olootl
rlow
104
-
2.2 0-Adrc~lucc~~tors
v:~socot~slriclion.Ilowcvcr. lllcre docs not appear
to bc a resting vasoco~~strictor
tone rncdiated
tliiortpl~lliis systctl~as renal tlenervalion does 1101
iricrcasc le~lal1)luutl flow (I)ernc, 1952). Exercise
is associatctl with cr-~~~ctliated
vasoco~istrictionwit11
$1 ~csultantclccrcasc in glv~ricrrllarfiltration rate arid
rcrinl I)lood flow (Swairisoi~ct d . , 1980). 'l'l~isretlr~ctioii is cvci~iliore ~)roi~outiced
wltei~the f12:iilr~cr~orel)tots
are blocked.
cr-Hlockiilg clrues slicli as prazvsin and plienoxyl)cttzar~~i~~c
have no eli'ect on renal blood flow
a1 rest h c c a ~ ~ sofc tile al)scnce of a 1o11cin renal
vesscls. Iloacvcr. tliese aRerlts d o llrevent a fall ia
rc~i;ilblootl flow r111derco~lditionswlicrc tr activity
is iticic;~sctl,sr~clias c;irdiac failu~c(Millard el al.,
1972). Cli~likcsonic utllcr fl-blocking agents, labct;iIo1. wllicli Ilas cr- as well as fl-l~lockingproperties,
tlocs tiot rcdilcc renal blood flow during exercise
(L:~rsen; I I I ~I'cderson, 1980).
0-Adret~oceptorsare subdivided into ol@.-receptors based on cliaractcristic responses lo
sy~npatlion~inlctic
nrliines (Lands et al., 1967). TIle
fll-rece1)tors nlctliate cardiostimulation and rerlin
rclcasc \vliilc (?a-rcccptors lllctlinte direct vasodila.
tation. 1Cc11in ~,roducesvasoconstriction tllrougll
aiipiotctisin 11. Ily dccreasi~~g
rcriin release. p,.
blockade tc~ltlsto increase renal blood flow. 0,Adrcnoceptors tilediate vasodilatation and l ~ a \ . ~
been dcn~or~slrated
i l l l l ~ erenal vasculature (Mark
el 31.. 1969).
111 addition to local actions on the reoal vasculaturc, [lie ovcrall renal liaetr~ody~~aniic
rcspolise
to 0-stitnulation or blockade deper~dson systcn~ic
c[lccts brotiglit about by el~angesin sympathetic
activity, oarticularly cardiac outprlt arid arterial
blootl pressure. In the clderly, rnallers are furtlrer
cot~~plicated
as tllere is decreased responsiveness to
bull1
and 0?-stiinulation (Dillon el al., 1980;
Vestal el al., 1979), and blockade (Conway et al.,
197 1) compared wit11 young adults.
In suinniary, tllc renal haet~iodynamicen'ects of
any 0-blocking agent are dilTicult to predict because of tlie large tluli~berof variables. Ilidividual
0-blocking drugs diUer in tlieir eKect on renal blood
flow because o r direrences in their selectivity and
added properties. Furtl~errnore,in tile elderly, respo~~sivct~css
is ditninisl~ed.
ol-
-
Placebo
1400.
t"
E
C7
.- 1200-
.1
1
.-C
E
L
-E
6
1 000
Aler~olol
L
3. l;[Tecls c?f fl-AJlvtrocc~)~or
Llloclci~~g
Dr~rgs011 l<erral13lood Flow in the
l'ourlg
.----/
l)ifi'erclices have been observed between tllc
renal haen~odynarnicerects of @-blocking drugs
wIieii given s h o i ~term by intravenous irijectiol~atid
when adn~inistcredorally long term. Such differcrices ~)robal)lyrcllccl pltysiological adaptation to
nlany ufthe acute cflccts during lorig ter111theral)!'
As atitiliypcrtcnsivc n~cdicationis taken long terrll.
tllc en'ects of 0-blocking drugs during long tern1
adtnii~istrationare more clinically releranl.
.-
.0
3.1 Sliort 'rertr~lt~traver~ous
Adn~iaistration
~0.05
I
'
I
Elleclive rerisl blood flow 111 10 elderly liyperlenslve
f)ntiei~ls
l"llowiilg 12 wreks' tienlment
placebo
sten0101.
Fiq. I.
In young patients, the ri~ajorityof 0-blockit%
drugs, irrespective of cardioselectivi~y,have bccll
sllowe to decrease renal blood flow followir~ginlraVCIIOUS a d ~ ~ ~ i n i s t r a t iThis
o ~ l . eficl llas been notcd
will1 ater~ololand ~acioprolol(Swainso11cl nl., 1980)
.t-Ulockersand
flerial
Blood Flow
as ncll as prol)ratlolol (Sullivan el al.. 1976) and
I ~ i ~ ~ d(Ilcic~li
o l ~ l el al.. 1977). I'llc average reducliu~lit1 rcrlal I>looti flow is about 12%. 111contrast
10 111c.s~
fintlings, ~ladololhas bee11observed to intrc:lse rc~lalblvod flow in a co~nbi~lation
of young
Ilr;lltl~yand I~yl)crtc~~sive
subjects on a low salt diet
(Ilollcl~berget al., 1979).
3.2 Long 'Tern1 Oral Ad~i~irlistratior~
105
25% illcrease in eKcctive renal blood flow, f r o n ~
512 to 646 111l/n1in/1.73m~
(p < 0.05) [fig. I]. During aterlolol tllerapy average mean arterial pressure
was reduced fro111 130mm Hg to 108ni1i1 I-ig (p <
0.001). There was no significa~~t
c l ~ a ~ ~ing eglorllerular filtratiol~,rate, wllile rneall scrutn creatin.
i ~ l elevels illcreased by an avcragc of 9% durinf
atcr~olollllerapy but re~nainedwitllitl the normal
range.
Lolip, tcrrii oral tllerapy wit11 propranolol 1.c4.2 Nadolol
d11ccs renal blood flow (Bauer ant1 Brooks, 1979;
O'L'o~lnorct al.. 1978) while 110 cllange was obI'llis was a rando~l~iscd,
single-blind, placebo.
cc~vcd wit11 l l ~ e IIVII-selectivedrug, all)~~er~olul,
controlled, crossover study in w l ~ i c l 10
~ elderl!
wl~icl~
II:IS 1)arti:il agorlist activity (Pctlcrscrl, I 9 75). I~yl)ertcrlsivepatients took part. Eacli phase lastec
I.illlc cc~~lclusive
evitlctlcc is available regarding tllc 10 weeks and efkctive rerial blootl flow was rlleas
rll'ccl or LVIIR tcrlll oral adtni~listrationof nadolol ured at the ctld of each pllase. Nadolol reducec
o11 rerl;il blood Ilow. Wanl-Ma~~ning
and I-lobs011 rc~lalblood flow by an average o r 20% fro111 5 5 !
(p < 0.005) [lig. 21. Averagc
(1980) Ibund no cl~angc.On the other 11a11tl.h i t - to 447 111l/111in/1.73rn~
rllearl arterial pressure was reduced frorn 133mn
I V I I et ;\I. (1980) fou~ltlthat renal blood flow intrr;lscd Ibllowiag rladolol in 5 of 6 patients with Ilg to 1 14111n1Ilg (p < 0.001) during liadolol treat
IIOI.III:II C : I I ~ ~ ~ oi111)11t
OC
wllcreas it fell in 2 patients tllcnt. Glo~llerularfiltration rate did not alter sip
wil11 initi;~llyl ~ i g lcardiac
~
output. Waal-blatl~~it~g
aificantly, nor did serulli creati~lit~c
or blood urea
and Uvlli (1980) fou~ldno cllar~gein re~lalblood
Ilow d u ~ . i ~lorlg
l g tern1 oral therapy with atetlolol.
Placebo
Ily~)crtcnsio~~
ill t11e elderly din'ers in rllally respccts fro^^^ hyl)erteesion in younger patients. Mcssc~lict aI. ( 1981) fou~idtllat elderly I~ypcrtcnsives
bad a lower cardiac index and itltravascular volllole and l~igllcrsystenlic vascular resistat~cctllati
mnlcl~cd your~g I~ypertensive patients. As 0nd~caoceptorresponsiveness in tlie elderly is 81lcrctl and tllcir re~ialfunction is reduced we obscrvetl tllc elfect of long lenii oral ad~llinistr
a 1'IVII
or ateaolol, rladolol and labetalol on blood pressure and effective renal blood flow in elderly
~l!~pcrtc~~sive
patietlls.
Nadolol
-
N
m
.600
3
0
ii:
73
0
m
K
a,
u
ar
h 400
U
a,
' f l ~ i swas a ra~ldolniseddouble-blind placcboculltrolled crossover study in wllicl~ 10 elderly
Il!~~crtcnsivepatients took part. Each pliase lasted
12 weeks. Effective renal blood flow was nleasured
at tllc end ofeacli phase fro111 the plasnia clearance
of ' ? J ~ - l ~ i p p u rand
a n a sinlultallcous haenlatocrit
"id glolll~rlll~r
filtration rate ~10111 tile plaS1lla
'Icararlcc of "Cr EDTA. Atenolol caused a tllcali
r.
W
~
- --
pcO.005
elderly hypertensiv
weeks' Irealrnenl wllh placebo and ni
i 2, ~~ ,l , ~ renal
~ l blood
l ~ ,low
~ in 10
pnlierits lollowing
dolol.
10
11-Blockers and Renal Blood Flow
-
1000-
Placebo
N
E
c9
b-
.
-
.-C
E
--.
-.
--.
:::. ----.
106
Labelalol
0--*
Elderly
---a
Young
-I.
800-
-
E
3
0
ii
600-
u
0
-0
-m
400-
w
n
w
BCl
w
Y.
w
-
=
200-
---
p:ns
Fig. 3. Elleclive renal blood flow In 9 elderly and 9 young
hypertensive patients lollowlng 12 weeks' treatment with placebo and labetalol.
4.3 Labetalol
Labetalol has a- and 8-blocking properties. We
cutnpared its effect on effective renal blood flow
during long term oral therapy in 9 elderly and 9
young hypertensive patients. It was a randonlised
single-blind placebo-controlled crossover study in
a7hicIieach phase lasted 12 weeks. Tliere was n o .
iignificant aheration in effective renal blood flow
it1 either age group (fig. 3), while mean arterial
xessure was reduced by 17mm Hg (p < 0.005) in
.Ite elderly group and 13mm Hg (p < 0.001) in the
/oung group. Glomerular filtration rate did not
:hange, nor did serum crealinine or blood urea.
Our findings reveal an improvement in renal
lood flow with atenolol, a reduction with nadoLol
nd no change with labetalol, during long term oral
lerapy in elderly hypertensive patients. Glomerlar filtration rate was maintained despite a reuction in arterial pressure. The difference beveen the drugs in their effect on renal blood flow
lay be explained at least in part by their selectivy. Atenolol blocks ~l-adrenoceptorsbut not B2ceptors, thus a corl~binationof reduced Dime-
diatcd vasoconstriction and unimpaired P2-medialed vasodilatation might result in an overall in.
crease in renal blood flow. Nadolol, on the other
hand, blocks P2-receptors, thus inhibiting renal
vasodilatation and reducing renal blood flow. La.
betalol, even though a non-selective blocking drug,
does not alter renal blood flow, as the tendency to
do so is offset by its a-blockade. The maintenance
of glon~erularfiltration rate with all drugs suggests
that autoregulation is less readily altered by 0blocking agents.
Our data suggest that selective 8-blocking drugs
increase effective renal blood flow in elderly
patients while non-selective agents may decreasc it.
However, as changes in glomerular filtration rate,
crcatinine and blood urea werc not clinically significant, the clinical importance of alterations in
effective renal blood flow in the present studies renlains to be elucidated.
..
Bauer, J.H. and Brooks. C.S.: The i6ng term effects orpropranolol
on renal function. American Journal of MediciFe 66: 405410
(1979).
Berne. R.M.: Haemodynamics and sodium excretion of the denervated kidney in the anaesthetized and unaesthctized dog.
American Journal or Physiology 171: 148-158 (1952).
Britton. K.E.: Grucnwald. S.M. and Nimmon. C.C.: Nadolol and
renal haemodynamics. Royal Society or Medicine, International Congress and Symposium Series No. 37: 77-86 (1980).
Conway. J.: Wheeler, R. and Sannerstedl, R.: Sympathetic nervous activity during exercise in relation to age. Cardiovascular
Research 5: 577-58 1 (1971).
Dillon, N.: Chung. S.: Kelly, J. and O'Malley. K.: Age and bcla
adrenoceptor function. Clinical Pharmacology and Therapeutics 27: 769-772 (1980).
tlcierli, C.: Thoelen. H. and Radiclovic. P.: Renal function Tollowing a single dose of pindolol in hypertensive patients with
varying .degrees of impairment of renal function. Inremational Journal of Clinical Pharmacology and Biopharmacy I %
65-71 (1977).
flollenberg N.K-;Adams, D.E.: McKinstry. D.N.: Williams. G.11.:
D O N C ~L.J.
~ . and Sullivan, J.M.: Beta adrenoceptor blocking
agents and the kidney: Effect ofnadolol and propranolol on
the renal circulation, British Journal of Clinical Pharmacology I (Suppl. 2): 219s-225s (1979).
Lands. A.M.; Arnold. A.: McAuliff, J.P.; Luduena. F.B. and Broun.
T.J. Jr: Dillirentiation o r receptor systems activated by sympathomimetic amines. Nature 214: 597-598 (1967).
Larsen. J.S. and Pedencn. E.B.: Comparison of the effecls of propranolol and labetalol on renal haemodynamics at rest and
during exercise in essential hypertension. European ~ o u r n a l
or Clinical Pharmacology 18: 135-139 (1980).
Mark, A.L.; Eckstein, J.W.: Abboud. E.M. and Wendling. t4.G.:
Renal vascular responses to isoproterenol. Amedcan ~ o u m a l
of Physiology 21 7: 764-767 (1 969).
Messerli. F.H.: Glade. L.B.; Dreslinski. G.R.; Dunn. F.G.: Resin.
E.; McPhn. A.A. and Forhlich, LD.: Hypertension in the
clderly: Haemodynamics. fluids volume and endocrine findings. Clinical Science 6I(Suppl. 7): 393s-394s (1981).
Millard, R.W.; fliggins, C.B.:.Franklin. D. and Vatner. S.F.: Rep
il-Dlock~lsand nelial Blood Flow
106
-
.- 1 0 ~ 0 -
Placebo
E
C)
I-.
7
-.'.
:-. - - - .
----:>.
UOO
Labelalol
-*Elderly
m.
*.
-
=---Young
..
E
-E
5
GOO-
iiI
XI
0
-0
-
"I
AO~I-
15
C
al
K
a)
bt) zoo
...al
w
A
--
p : 11s
diatcd vasocoristriction and uriin~paired P2-mediated vasodilatation niigl~tresult in a n overall illcrease in renal blood flow. Nadolol, on tile otller
I~and,blocks P2-receptors, thus i~iliibitingrenal
\rasodilatation and reducing renal blood flow. La.
bctalol, even tllougll a non-selective blocking drug,
rlocs not alter renal blood flow, as tlie t e ~ ~ d e n c10y
do so is omset by its a-blockade. T l ~ enlaintenarice
of glornerular filtration rate with a11 drugs suggests
that autoregulation is less readily altered by 0blocking agents.
Our data suggest that selective &blocking drugs
increase elkclive renal blood flow in elderly
p a t i e ~ ~wl~ile
t s non-selective agents may decrease it.
Ilowever, as cllariges in glornerular fillration rate,
crcatinine and blood urea were not clinically siknificant, \lie clinical in~l)ortanceof alterations in
cfl'cctive renal blood Ilow in tlie present studies reniairis to be elucidated.
l~efere~~ces
F i g . 3. Ef'ec'ive
'lowIn elderly I % ~ young
~
tlypertocislve paliotits lollowlng 12 weeks' treatnlent with placobo slid labetalol.
4.3 Labetalol
hbctalol llas n- and 0-blocki11g propcrlics. We
cunil)arcd its efl'ect on efi'ective renal blood flow
during lollg tern1 oral tllerapy in 9 elderly alld 9
yot111g11).~1crtc11sive
patielits. 11 was a randolllised
single-blind p l a c e b o - C O I I ~crossover
~ O ~ ~ study ill
mtliicli each pliase lasted 12 weeks. Tliere was no
;igllificalltalteration in eflective rellal blood flow
,11 ci,ller
group (fig. 31, wllile Incan
7lcssure was reduced by 17n1111 llg (P < 0.005) in
Ilc elderly ~ r o u l and
)
13moi klg (p < 0.001) in the
toung group. Glolllerular filtratioll rate did not
:Ilange, nor did serum crealinine or blood urea.
5.
~ ~ ~ S C I ~ S S ~ U ~ I
Our f i l l d i ~ sreveal an illlprovetnent in rerial
h o d flow wit11 atenolol-, a reduction with nadoLol
lid 110 cllallge willl labelalol, during long tertn oral
lerall)' ill elderly llypellcllsi~epatients. G I ~ m e r Inr fillration rate was maintained despite a reuction in arterial pressure. The diflerencc bevccll \lie <irugsill tlleir
on renal blood flow
lay \K ell)lailled
Bast in
by tlleir Selecti,,y. Atenolol blocks 01-adr~~ioceptors
but 110t 02Cel~loSS,Ill11s a con~biriatioriof reduced P,-nle-
Uauer. J.ll. and Brooks. C.S.: The I& t c r ~ iefrccts
i
orpropranolol
on renal
~unclion.
American ~~~~~~l
or ~ ~ d i66:~ 405-410
i ? ~
( 1979).
Ucrne. R.hl.: Ilaeniodynaniics and sodium excretion or the d e
nervated kidney in the anaesthetized and unaesthetizcd dog.
Alncrican Journal of Physiology 171: 148-158 (1952).
Dritton. K.E.: Grucnwald. S.M. and Ninin~on.C.C.: Nadolol and
rcnal liaemodynamics. Royal Society of Medicine. Interna.
tional Congress and Symposium Series No. 37: 77-86 (1980).
Conway. J.: Wheeler. R. and Sanncrstedt. R.: Sympathetic new
ous activity d u r i n ~
exercise i n relation to age. Cardiovascula!
Rcscarcli 5: 577-581 (1971).
ill^^^. N.: ~
h s,: ~
~ ~J.~land
l (~
~ y ,~
~ ~K.:
l, ~
l ~
g and
e~ bet7
.
,~,cnocepto~ function. CIillicaI pttar~nacologyand Therapcu
tics 27: 769-772 (1980).
Ileierli. C.: Thoelen. H. and Radielovic. P.: Renal runction rol
Ivwinga single dose of pindolol in Iiypertensive patients will
varying degrees of impsirnient of renal runction. lnlema
tional Jot~rnalorClinical Pliartnacology and Biophan~iacy1s
65-71 (1977).
Ilollcnlx~p.N.K-; Adams. D.E.: McKinstry. D.N.; Williams. G.11
Domcki. L.J. and Sullivan, J.M.: Beta adrenoceptor blockill:
ngcnls nnd the kidney: Errect of nadolol and propranolvl 09
the renal circulation, Brilish Journal of Clinical Pharmacol
ogy 1 (Suppl. 2): 219s-225s ( 1 979).
Lands. A.M.: Aniold. A,: McAuliK, J.P.: Luducna. F.13. and I3rosr
T.J. Jr: Dillirentiation or receptor systems activated by syn'
pattiv~nimeticamincs. Nature 214: 597-598 (1967).
hrsen, J.S. and Pcdersen. E.R.: comparison orthe CITCCIS of prc
~)rat~olol
and laktalol on renal haemodynamics at rest an
d u r i ~ ~exercise
g
in essential hypertension. European Journ:
of Clinical Pharmacology 18: 135-139 (1980).
~
~I\,L,:~ ~ k~ ,kJ.w.:
~~ ~
b b ~~ E.M.
~i d and
~, Wendling.
,
M.(;
R,,,~I vascu~a, responses to isopro~erenol.
Anic$an Journ:
o f PIiysioIogy 217: 764-767 (1969).
h~esse~li.
F.14.: Glade. L.B.; Drcslinski. G.R.; Dunn. F.G.: Resic
E.: McPbee, A.A. and Forhlicli, ED.:Hyvne-ion inI'
cltlcrly: Ilacmodynamics. fluids volume and endocrine 1%'
ines. Clinical Science 6I(Suppl. 7): 393s-394s (1981).
Millard, R.W.: Iliggins, C.B.;.Franklin. D.and Vatner. S.F.: Rc
d-Blockers and Renal Blood Flow
ulation o f t l i e renal circulation during severe exercise i n nornial dogs and dogs with experimental heart failure. Circulation Research 31: 881-888 (1972).
O'Connor 1J.T.: Preston. R.A. and Sasao, E.H.: Renal perfusion
changes during treatment o r essential hypertension: Prazosin
wrs1r.t propranolol. Journal o f Cardiovascular Pharmacology
I (Suppl.): S38-S42 (1978).
Fcdcrsen. E.B.: tilonierular filtration rate and renal plasma flow
i n patients with essential hypertension before and aner treatnlcnt with alprenolol. Acta Mcdica Scandinavica 198: 365371 (1975).
Rector. J.13.; Stein. J.11.: Day. W.H.; Osgood. R.W. and Ferriss.
T.F.: Erect o f haemorrliage and vasopressor agents on distribution of renal blood flow. American Journal oTPhysiology
222: 112.5-1131 (1972).
Sitilpson. F.O.: Ueta adrencrgic receptor blocking drugs i n hyper7: s85-105 (1974).
tension. D r r ~ ~
Sullivan. J.M.: Adatns. D.P. and llollenberg, N.K.: Beta adrcnereic blockade i n essential hypertension: Reduced renin release despite renal vasoconstriction. circulation Research 39:
532-536 (1976).
Swainson. C.P.: Robson. J.S. and Goodfellow, R.M.: ElFect o f beta
adrenergic blockade o n renal function during exercise. Seventh Scientific Meeting o f ISII. New Orleans (1980).
Tudor Ilart, J.: Occasional paper: Journal o f the Royal College
o f General Practitioners 12: 11-12 (1980).
Vestal. R.E.; Wood, A.J.J. and Shand. 0.0.:
Reduced beta
adrenoceptor sensitivity i n the elderly. Clinical Pharmacology
and Therapeutics 26: 181-186 (1979).
Waal-Manning. H.J. and Bolli. P.: Atenolol vs placebo i n m i l d
hypertension: Renal, metabolic and stress antipressor elFects.
Dritish Journal o f Clinical Pharmacology 9: 553-560 (1980).
Waal-Manning. t1.J. and Hobson. C.H.: Renal function i n patienu
with esscntisl hypertensioN receiving Nadolol. British Medical Journal 3: 423-424 (1980).
Wilkinson. R.: 8-Dlockers and renal runction. Drugs 23: 195-206
(1982).
Author's address: Prof. K. O'Malley. Department o f Clinical
I'harniacology. Royal College o f Surgeons i n Ireland, Dublin (Eire).