THE STIMULUS TO HYPERTROPHIC GROWTH
113
C. Experiments Concerning the Stimulus to Hypertrophy
There have been a number of attempts to demonstrate that the kidney
hypertrophy which follows unilateral nephrectomy is the result of the
elevated functional activity of the remaining kidney. The rate of compensatory hypertrophy is increased after anastomosis of the ureter of the
intact kidney to the duodenum so that most of the urinary waste is reabsorbed (Bollman and Mann, 1935). If the bladder of an otherwise intact
dog is anastomosed to the ileum, the kidneys hypertrophy (Hartman,
1933). Restriction of blood flow to the remaining kidney and food and
water restriction after unilateral nephrectomy reduce the rate of hypertrophy in dogs and rats (Block et al, 1953; G. E. G. Williams, 1962b). The
difficulty in interpreting these results is that most of the animals had
pathological conditions which eventually resulted in death, probably from
poisoning by urinary constituents in the blood.
The injection of urea into a unilaterally nephrectomized mouse is reported to have no effect on the rate of hypertrophy (Semenova, 1964).
Ligature of one ureter results in a hypertrophic response in the ligated
kidney, but no response in the intact partner (Benitez and Shaka, 1964;
Ewald and Mason, 1963; Idbohrn and Muren, 1957). Anastomosing one
ureter to the duodenum in otherwise intact dogs has been reported to have
no effect (Block et al, 1953), occasional hypertrophic effects (Fortner and
Kiefer, 1948), or bilateral hypertrophy for 2 months followed by atrophy
of the anastomosed kidney and hypertrophy of the partner (Hinman,
1923). Cutting one ureter, so that all the urine excreted by one kidney is
reabsorbed from the peritoneal cavity, causes no renal hypertrophy (Ewald
and Mason, 1963; Goss and Rankin, 1960; D. P. Simpson, 1961a). If the
nonfunctional mesonephros is removed from one side of a chick embryo,
the tissue remaining on the other side shows a hypertrophic response
(Weiss, 1955). Increased excretory function is clearly inadequate to explain
the stimulus to hypertrophic growth in the kidney following unilateral
nephrectomy, although extremely elevated levels of urinary constituents
in the body fluids may sometimes have a hypertrophic effect.
The injection of kidney macerate has been reported to have a stimulatory
effect (Breuhaus and McJudkin, 1932), no effect (Cameron and Kellaway,
1927), or an inhibitory effect (Goss, 1963; G. E. G. Williams, 1962a) on
kidney hypertrophy. However, Williams noticed that rats injected with
kidney macerate had a reduced food intake, and the effects of the injection
could be produced by starvation alone. Andres (1955) demonstrated in
chick embryos a dramatic increase of the ratio of mitotic index in mesonephros to mitotic index in liver after injection of macerated mesonephros
tissue. The reciprocal effect was obtained with liver macerate. Weiss (1955)
treated embryonic kidney cells in tissue culture with extracts of whole
113
C. Experiments Concerning the Stimulus to Hypertrophy
There have been a number of attempts to demonstrate that the kidney
hypertrophy which follows unilateral nephrectomy is the result of the
elevated functional activity of the remaining kidney. The rate of compensatory hypertrophy is increased after anastomosis of the ureter of the
intact kidney to the duodenum so that most of the urinary waste is reabsorbed (Bollman and Mann, 1935). If the bladder of an otherwise intact
dog is anastomosed to the ileum, the kidneys hypertrophy (Hartman,
1933). Restriction of blood flow to the remaining kidney and food and
water restriction after unilateral nephrectomy reduce the rate of hypertrophy in dogs and rats (Block et al, 1953; G. E. G. Williams, 1962b). The
difficulty in interpreting these results is that most of the animals had
pathological conditions which eventually resulted in death, probably from
poisoning by urinary constituents in the blood.
The injection of urea into a unilaterally nephrectomized mouse is reported to have no effect on the rate of hypertrophy (Semenova, 1964).
Ligature of one ureter results in a hypertrophic response in the ligated
kidney, but no response in the intact partner (Benitez and Shaka, 1964;
Ewald and Mason, 1963; Idbohrn and Muren, 1957). Anastomosing one
ureter to the duodenum in otherwise intact dogs has been reported to have
no effect (Block et al, 1953), occasional hypertrophic effects (Fortner and
Kiefer, 1948), or bilateral hypertrophy for 2 months followed by atrophy
of the anastomosed kidney and hypertrophy of the partner (Hinman,
1923). Cutting one ureter, so that all the urine excreted by one kidney is
reabsorbed from the peritoneal cavity, causes no renal hypertrophy (Ewald
and Mason, 1963; Goss and Rankin, 1960; D. P. Simpson, 1961a). If the
nonfunctional mesonephros is removed from one side of a chick embryo,
the tissue remaining on the other side shows a hypertrophic response
(Weiss, 1955). Increased excretory function is clearly inadequate to explain
the stimulus to hypertrophic growth in the kidney following unilateral
nephrectomy, although extremely elevated levels of urinary constituents
in the body fluids may sometimes have a hypertrophic effect.
The injection of kidney macerate has been reported to have a stimulatory
effect (Breuhaus and McJudkin, 1932), no effect (Cameron and Kellaway,
1927), or an inhibitory effect (Goss, 1963; G. E. G. Williams, 1962a) on
kidney hypertrophy. However, Williams noticed that rats injected with
kidney macerate had a reduced food intake, and the effects of the injection
could be produced by starvation alone. Andres (1955) demonstrated in
chick embryos a dramatic increase of the ratio of mitotic index in mesonephros to mitotic index in liver after injection of macerated mesonephros
tissue. The reciprocal effect was obtained with liver macerate. Weiss (1955)
treated embryonic kidney cells in tissue culture with extracts of whole