No.
4783 July 1, 1961 NATURE
of administration was either intraperitoneal or by
stomach tube.
Two days after completion of the vitamin treat-
ment the phagocytic activity was measured in each
group of animals by the rate of disappearance of a
known amount of specially prepared carbon from the
circulating blood•, the procedure used being that
described in a previous communication•, and the
total body phagocytic activity or phagocytic index
being denoted by the symbol K.
Ten control animals, receiving no treatment,
showed a phagocytic index or K value of 15 ± 2 ·O.
The results are shown in Table 1. In the doses
administered the vitamins given to normal healthy
growing mice had no discernible effect on the phago-
cytic activity of the reticulo-endothelial system. The
above results might well have been expected since,
for the most part, vitamin action appears to be
related to the enzyme systems of normal cellular
metabolism. In contrast, in infection, when the
metabolism of the reticulo-endothelial cells increases,
the requirement for the various vitamins may also
be raised.
In these investigations we gratefully acknowledge
advice and gifts of vitamins from Roche Products,
Ltd., and Glaxo Laboratories, Ltd., and also financial
assistance from the Tobacco Manufacturers' Standing
Committee and the Medical Research Council.
J. CORDINGLEY
T. NICOL
Department of Anatomy,
King's College,
London, W.C.2.
'Nicol, T., Helmy, I. D., and Abou-Zikry, A., Brit. J. Surg., 40, 166
(1952).
'Sewell, I. A., and Nicol, T., Nature, 181, 1662 (1958).
• Nicol, T., and Sewell, I. A., Nature, 184, 1241 (1959).
• Nicol, T., Snell, R. S., and Bilbey, D. L. J., Brit. Med. J., ii, 800
(1956).
• Spector, W. S., Handbook of Biological Data, 1, 197 (W. B. Saunders
Co., Philadelphia, 1956).
• Biozzi, G., Benacerraf, B., and Halpern, B. N., Brit. J. Exp. Path.,
34, 441 (1953).
Effect of Bradykinin on Uterine Activity
IT was reported recently' that plasma kinin is
formed spontaneously in human plasma collected
during labour. Tested on the isolated rat uterus, the
maximum oxytocic activity was stated to be equiva-
lent to several units of oxytocin per millilitre of
plasma. It was suggested that kinin formation may
be related to the powerful contractions of the human
uterus during parturition.
As yet the only kinin which has been chemically
defined and is available in a pure form is bradykinin.
We therefore investigated the uterine effect of
synthetic bradykinin• on the human uterus in sitn
(external3• 4 and internal5 tocography) and in vitro•,
and on the uterus in situ of aruesthetized non-
pregnant rats, cats 7 and rabbits•.
Single intravenous injections of up to 2 µgm./kgm.
bradykinin and intravenous infusions of 0·14, 0·28 or
0 ·56 µgm./kgm./min. of bradykinin--each dose
infused for a period of 5 min.-had no oxytocic effect
on the human uterus in situ a few hours before or after
labour. In one case, l ·4 µgm./kgm./min. infused for
3 min. was followed by a contraction, which may have
been connected with the administration of the pep-
tide. Although no uterine effect could be detected,
the administration of higher doses of bradykinin
© 1961 Nature Publishing Group
83
elicited a number of symptoms, such as lowering of
the systemic blood pressure, hot flushes, sensation of
warmth in various parts of the body, etc.
Isolated strips of human myometrium obtained at
Cresarian section contracted only after bradykinin
doses as high as several hundred or even thousand
µgm./1. Somo strips failed to respond even to 10,000
µgm./1., although their sensitivity to oxytocin
('SyntocinonR'), for example, 25-100 milli-units/1.
was normal (100 milli-units oxytocin is equal to 0 ·2
µgm. peptide).
The rat uterus in situ usually gave a short-lived
contraction with 100 µgm./kgm. bradykinin (intra-
venous); 10 µgm./kgm. elicited a response only in a
few animals. 100 milli-units/kgm. oxytocin consis-
tently produced a response in all the rats.
In the cat uterus in situ 100 µgm./kgm. bradykinin
(intravenous) invariably elicited a short-lived re-
sponse. In many animals 33 µgm./kgm. or 10 µgm./
kgm. was also effective, and one responded to as little
as 3 ·3 µgm./kgm. All the cats displayed a character-
istic uterine reaction to 40-80 milli-units/kgm. of
oxytocin.
The sensitivity of the rabbit uterus in situ to brady-
kinin varied greatly. Whereas in some rabbits the
intravenous injection of 1 or 10 µgm./kgm. was
followed occasionally by a brief contraction of the
uterus, others did not react even to 100 µgm./kgm.
(intravenous). All rabbits showed a normal sensi-
tivity to methyl-ergometrine ('MetherginR') : O· 15
mgm./kgm. invariably elicited the usual uterotonic
reaction.
The isolated rat uterus is known to have a very high
sensitivity to bradykinin : a minute dose of O·00003
µgm./ml. will sometimes elicit a contraction•.
However, the findings presented in this communica-
tion show that bradykinin can scarcely be regarded as
oxytocic in the usual sense of the word. The doses of
bradykinin required to elicit a contraction of the rat,
cat and rabbit utenlS in situ are usually much higher
than those evoking a marked fall of blood pressure.
Moreover, the contraction is of a shape different from
that produced by a low dose of oxytocin. The amounts
of bradykinin which contract the isolated human
myometrium are extremely high, and on the human
uterus in situ bradykinin is virtually devoid of any
effect, even in doses producing considerable distress.
These findings do not favour the view that brady-
kinin might be a physiological oxytocic factor respon-
sible for increased uterine activity during labour in
the human being.
B. BERDE
Pharmacological Laboratories,
Sandoz, Ltd.,
Basle.
K. SAAMELI
Department of Obstetrics and Gynrecology,
Cantonal Hospital,
St. Gall, Switzerland.
1
Armstrong, D. A. J., and Stewart, J. W., Nature, 188, 1193 (1960).
'Boissonnas, R. A., Guttmann, St., and Jaquenoud, P.-A., Helv.
Chim . .Acta, 43, 1349 (1960).
• Bainbridge, M. N., Nixon, W. C. W., Schild, H. 0., and Smyth,
C. N., Brit. Med. ,l., i, 1133 (1956).
• Smyth, C. N., J. Obstet. Gynrec. Brit. Emp., 64, 59 (1957).
• Caldeyro-Barcia, R., and Poseiro, J. J., Olin. Obstet. and Gynec.,
3, 386 (1960).
• Berde, B., and Saamell, K., .A.eta Endocrinol., 32, 391 (1959).
'Berde, B., Doepfner, W., and Konzett, H., Brit. J. Pharmacol.,
12, 209 (1957).
• Rothlln, E., Schweiz. med. Wschr., 68, 971 (1938).
• Konzett, H., and Sturmer, E., Brit. J. Pharmacol., lli, 544 (1960).