Transcellular active tubular transport of organic cations occurs in the proximal renal tubule in the direction of excretion. These organic cations may be primary, secondary, tertiary, or quaternary amines. Endogenous neurohumors such as choline and catecholamines and drugs such as morphine and tetraethylammonium are representative transportable organic cations. Competitive inhibition for transport is found among organic cations. Organic anions, however, do not compete for this transport. Organic cations used as drugs may interact with the transport of endogenous organic cations to alter the excretion patterns of both. Bidirectional active tubule transport can be demonstrated for choline and is accompanied by simultaneous renal metabolism of choline. Studies using vesicles prepared from luminal and antiluminal membranes of renal cortex suggest that organic cation transport occurs in both vesicle preparations. However, only the luminal vesicles showed the characteristics of carrier-mediated uphill transport.
Simultaneous accumulations in renal cortical slices of tetraethylammonium and p-aminohippurate were studied. Slices were obtained from fetal puppies and newborns. Newborns were sacrificed at intervals from birth to 9 weeks. Slice-to-medium ratios (S/M) were compared for adult, pregnant, and postpartum dog renal slices. Newborn piglets' kidneys were studied similarly. It was found that these two transport systems developed independently in the fetal and newborn puppy. The transport of TEA was low at birth and progressively rose to the adult value at 9 weeks. The PAH transport system was active in fetal and newborn tissues. Transports of both TEA and PAH were absent under anaerobic conditions. Acetate stimulated TEA and PAH slice uptakes to the same extent as in the adult. In the piglet the surface slice of the kidney showed low transports of TEA and PAH for the first 2 weeks. At 4 weeks both transport systems increased to equal those in the slices of the lower cortex. The lower cortical slices accumulated TEA and PAH from birth to 8 weeks of age at a fixed rate. The TEA S/M in the piglet at birth was more than twice that in the dog. PAH was accumulated in a predominantly conjugated but unidentified form in the piglet kidney slice.
In the mature foetal lamb most of the blood which reaches the coronary arteries comes from the inferior vena cava through the foramen ovale. A substance injected into a femoral vein will be carried up into the inferior vena cava, and be diluted with a large quantity of blood returning from the placenta; about two-thirds will pass to the left atrium, and one-third to the right atrium (Dawes, Mott & Widdicombe, 1954). The two-thirds which passes into the left atrium will be still further diluted with blood returning from the lungs, and will then be ejected from the left ventricle into the aorta, whence a small fraction may reach the coronary vessels. But a substance injected into a jugular vein will not reach the coronary arteries until it has passed through the lungs, the placenta or the lower part of the foetus.These considerations led to the hypothesis that substances such as adrenaline and acetylcholine, which are readily destroyed in animal tissues, should have a different effect upon the foetal heart rate and blood pressure according to the route of injection. This paper describes observations which were made to test this hypothesis in lambs of different gestational ages, and also describes some effects of sympathetic amines upon umbilical blood flow.
METHODSFifteen mature foetal lambs ( >132 days gestation) and ten immature foetal lambs (67-1 10 days gestation) were used. Pregnant ewes, mainly of a Clun-Hampshire cross-breed, but including a few Kerry Hill, were anaesthetized with sodium pentobarbitone. The initial intravenous injection was supplemented by an intravenous infusion of about 10-20 mg/kg/hr, sufficient to keep both ewe and lamb lightly anaesthetized. The lamb was delivered by Caesarean section and laid on a small warm table so arranged that the umbilical cord was not under tension.The blood pressure of the ewe was recorded by a mercury manometer from a carotid artery. The blood pressure of the foetus was recorded by a condenser manometer from a femoral artery. In the
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