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KMID : 0378019610040020117
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New Medical Journal
1961 Volume.4 No. 2 p.117 ~ p.156
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The Antidiuretic Activity in Serum of Patients with Essential Hypertension
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Abstract
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Antidiuretic hormone(ADH) is known to have a vasopressor action as well as an antidiuretic one. However, it is usually denied that the vasopressor effect of the antidiuretic hormone has physiological significance. This assertion is usually based on the argument that the amount of the hormone required to affect blood vessels is much greater than~is commonly believed to be secreted from the gland. A few milliunits of the hormone produce the antidiuretic effect whereas a thousand times that dose is necessary to elicit the vasopressor effect. Since the effect of posterior pituitary extract on the circulation was first described by Oliver and Schaefer in 1895, a voluminous literature has accumulated concerning the pressor effect of ADH. Numerous investigators have shown that hemorrhage provokes an antidiuretic response. According to observations made by Ginsburg and Heller, following hemorrhage there is a discharge of ADH from the posterior pituitary in amounts sufficient to aid in the maintenance of the. blood pressure: The amount of ADH in the blood of animals undergoing experimental hemorrhage correlates well with the changes in the blood pressure. With this experimental evidence, Ginsburg and Heller postulated . that ADH from the neurohypophysis is physiologcally significant playing an important role in the regulation of the blood pressure. Miller, et al. ´ described an increased antidiuretic activity observed in the serum of hypertensive patients. Stavrasky´s interesting experiment demonstrated that either an intact posterior pituitary or administration of pitressin is essential for the full pressor response of cats to intravenous epinephrine.
Female albino rats, weighing 150-200 gm., were fed on the National Laboratory of Chemistry stock- diet and housed under identical conditions. Each rat, at the end of a 16 hour period without food but supplied with water, received through a polyethylene gastric tube 1.0 milliliter of a 2% NaCl solution per 100 gm. of bcdy weight. This was repeated three times at hourly intervals. Immediately after the third oral hydration, an indwelling urinary catheter was inserted, and the amount of urine excreted every minutes was determined. Sera or pitressin were then injected intraperitoneally at the time when the five minutes urine volume was the greatest. This usually occured at about 80 minutes after the initial urinary bladder catheterization. Determination of the urine volume in 5 minute periods was continued until the volume was less than 0. 1 milliliter during 5 minutes. Initially injection of (1) pitressin (Park-Davis), (2) normotensive, healthy human adult serum, (3) starved (restriction of food and water) normotensive, healthy adult serum, and (4) starved rabbit serum were studied. Injection of more than 0.8 unit of pitressin induced a marked antidiuretic response which suppressed the urinary output to almost zero. Pitressin in smaller doses ranging from 0.6 to 0.3 unit induced a milder antidiuretic response in proportion to the dose used. Less than 0.3 unit of pitressin failed to induce any antidiuretic response. Normotensive, healthy adult human serum in the amount of one milliliter induced no inhibition of urinary excretion. Whereas similar doses of sera from starved, normotensive, healthy humans and from starved rabbits produced a marked antidiuretic response.
A marked antidiuretic activity was observed when one milliliter of serum from a patient with essential hypertension was injected; this effect was lost after the patient´s blood pressure was maintaind at normal levels for more than two weeks by antihypertensive drugs.
Antidiuretic hormone (vasopresson) is inactivated by various tissues and organs in vivo and in vitro as documented by the extensive studies of many investigators. Liver, kidney, spleen and nonpregnant uterus are known to be inactivating organs of ADH.
The author further studied experimentally the effect of the antidiuretic substance in the serum of patients with essential hypertension when injected into splenectomized female rats.
One group of female rats were splenectomized and another underwent laparotomy without splenectomy to serve as the control group. Seven days after the operation the rats were injected with one milliliter of the serum.
Serum of patients with essential hypertension exerted little or no antidiuretic effect on the splenectomized rats in contrast to the same marked effect as seen in the non-splenectomized control rats. Serum from rabbits after food and water restriction for 2 days also produced little or no antidiuretic effect on the splenectomized rats, whereas a marked antidiuretic effect was demonstrated in the non-splenectomized rats comparable to the effect seen in normal rats.
The author concludes from these studies that the antidiuretic activity of serum from patients with essential hypertension is correlated with the degreee of hyperten3ion. The 1 igher the blood pressure, the more marked is the antidiuretic effect of the serum when studied in the biological experiment described. In splenectomized rats, serum, shown to have antidiuretic activity in normal rats, failed to produce this effect. One might assume that splenectomy exerts a stimulating effect on the other ADH inactivating organs such as the liver and kidney,
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