Eric Ogden

Rise of Blood Pressure During Ischemia of the Gravid Uterus.

To test the concept that diminished uterine blood supply might play some part in the hypertension of eclampsia 1 the carotid blood pressure was recorded in acute experiments while the aorta was partially occluded below the renal arteries. Ten animals anesthetized with chloretone, with morphine and pen-tobarbital sodium, or by decerebration under ether were used. Six were pregnant (5 dogs, 1 cat); 4 were non-pregnant controls. The carotid and femoral blood pressures were recorded kymo-graphically and a long-handled screw clamp was adjusted around the aorta just below the renal arteries. The incision was closed with the clamp handle protruding and the animal was left undisturbed until the blood pressure was stable. The clamp was then tightened until the femoral pressure fell to about half its previous value and the carotid pressure was followed (Table I). In the non-pregnant control animals aortic compression was not followed by any change in carotid pressure other than the immediate adjustments discussed by Brotchner. 2 Rytand, 3 Brotchner, 2 and Goldblatt, Kahn, and Hanzal 4 have all pointed out that there is no progressive increase of arterial pressure after constriction of the aorta below the renal arteries. In 4 of the 6 pregnant animals aortic compression was followed by a definite gradual rise of blood pressure; in the other 2 the rises were small (16 mm in 2 hours and 24 mm in one hour respectively). The rises were so gradual that one could not usually say exactly when they began. The rises under chloretone were clear-cut and amounted to 10-58 mm but no strictly hypertensive levels were reached, perhaps because of the very low initial values. In the animal under morphine and nembutal the blood pressure was more normal but the rise was small.

The effect of pregnancy on experimental hypertension

Abstract To shed light on factors possibly concerned with the unfavorable influence of pregnancy upon human hypertension, rats and rabbits with experimental hypertension were studied during pregnancy or pseudopregnancy with deciduomas. Blood pressures were measured in rats by the tail plethysmograph and in rabbits by the ear capsule method. Hypertension was induced by partial ligation of renal arteries, or in some rats by painting one kidney with collodion and removing the opposite kidney later. Deciduomas were induced by placing silk threads in the uterine mucosa during pseudopregnancy. During pregnancy in normal rabbits, the changes in blood pressure as shown by these methods are negligible. Renal ischemia produced during pregnancy was followed by hypertension, but the onset was delayed until after delivery. Pregnancy produced an early fall in blood pressure in all of 10 hypertensive rats and a less constant fall in 12 hypertensive rabbits. No untoward effects were observed. An increase of protein content in the diet caused sickness or death in hypertensive nonpregnant rabbits. Pseudopregnancy with deciduomas in all of 11 hypertensive rats caused a decline in blood pressure corresponding roughly in time and extent with that caused by pregnancy. These findings suggest that the cause for the blood pressure fall observed more likely results from endocrine changes than from any action of fetal kidneys. Doubt is thrown on the concept that a “load on the maternal kidneys” plays a significant part in the exacerbation of hypertension usually observed in human pregnancy.

Renin-Like Substance in Blood after Hemorrhage.∗

Discussion and Conclusions The observed phenomena are consistent with the concept that the blood of the normal animal, with normal pulse pressure, contains activator but no renin whereas blood taken after hemorrhage when the pulse pressure may be low contains demonstrable amounts of a renin-like substance. Moreover, since the gut always responds slowly to posthemorrhagic blood, it seems likely that this blood contains a diminished amount of activator, since the usual response to a mixture of renin and activator is prompt. Prehemorrhagic blood, which according to this concept contains no renin is incapable of sensitizing the gut to either pre- or posthemorrhagic blood. The results in the single exceptional experiment already cited might be explained by assuming a low renin activator or high renin inhibitor content in the normal blood of the animal in question. If, as it appears, the renin content of blood increases after hemorrhage, when the effect of such an increase would help restore the blood pressure to normal levels, these findings support the view that the kidney acts as an organ of internal secretion, preserving the homeostasis of the whole circulatory system by a humoral mechanism. The assay method here described is not specific for renin or renin activator and further experiments to make the identity of the active substances involved more certain are in progress.

Restoration of Blood Pressure by Renin Activator After Hemorrhage.

Conclusions Injection of a renin-activator preparation of ox-plasma restored the blood pressure of dogs after hemorrhage. This restoration was observed with quantities of the preparation containing only one-tenth or less of the total plasma protein removed. Corresponding quantities of 10% gelatin or of control plasma concentrations failed to restore the blood pressure. From these observations it is concluded that the secretion of renin in severe hemorrhage (and perhaps in other forms of shock) is sufficient to produce exhaustion of renin activator. The resulting failure of the renopressor system is followed by a fatal collapse of blood pressure. This collapse may be staved off and the blood pressure restored by replacing the exhausted activator by a suitable preparation of ox plasma. These investigations suggest the possibility of improving the transfusion therapy of hemorrhage and shock by fortifying the plasma with suitable preparations of renin-activator, or possibly by substituting relatively small quantities of activator preparations for plasma in emergency treatment. Work in this direction is in progress.

Inhibition of Water Diuresis by Amytal

Recently Fee 1 has shown that the water diuresis, established in decerebrate dogs by administration of water through the stomach tube, is checked by the administration of chloroform, ether, chloralose, or morphine in the doses commonly employed to produce anesthesia or analgesia. The inhibition lasts, roughly speaking, for the same length of time as the narcotic effect. The technique given in the paper referred to, has been followed exactly in the 6 experiments reported here with the exception that intraperitoneal amytal was used instead of the drugs previously employed. In all cases the full dose (0.05 gm. per kilo) produced an immediate and lasting inhibition, complete as regards the excess water elimination. In the only two cases where measurements were made at minute intervals, the diminution in urine flow began during the second and third minutes respectively, following the injection of amytal. In one experiment the excretion was followed for over 10 hours and no recovery was observed. The following are the records of 2 typical experiments, the measurements being expressed graphically: No explanation is offered for the rise in curve I (marked X) but a similar rise was also noted in another experiment. The partial inhibition observed after the first injection in curve II has been observed with a dose as little as 1/10 gm. in a 6 kilo dog.

Blood Pressure of Pregnant Rabbits and its Response to Pitressin.

Schockaert and Lainbillon 1 have demonstrated that women in the latter half of a normal pregnancy are relatively insensitive to the pressor action of the postpituitary hormone, and that the blood serum of such women, when mixed with postpituitary hormone has an inhibitory action on the pressor coniponent as compared to the serum of non-pregnant ivonien. These findings have been applied to the study of human eclampsia. 2 This reports an attempt to determine whether such a phenomenon may be demonstrated in the rabbit. We have found no reports of blood pressure records throughout pregnancy except for the human being, and it was necessary therefore to determine whether iioriiial pregnancy in the rabbit produced any significant alteration of blood pressure. At various intervals through-out pregnancy, a standard dose of pitressin was administered intra-venously to the unanesthetized animal to obtain the pressor response. The method of Grant and Rothschild 3 was used for measuring the blood pressure on the central artery of the ear of warm, unanes-thetized female rabbits weighing 3 to 4 kg. In one major respect our technic differed from theirs. Measurements were made at intervals of 10 to 15 seconds rather than 1 or 2 minutes. This offered a necessary advantage in enabling us to follow the rather rapid changes of blood pressure which follow the injection of pitressin. By actual tests it was found that the reactive hyperemia resulting from rapid determinations caused a lowering of the blood pressure only on the second reading and not thereafter. Readings were made until 5 consecutive values were found within 4 mm. The mean of these 5 readings was recorded as the resting blood pressure. Pitressin was injected into the marginal vein of the ear opposite from the blood pressure capsule.

Dilatation of the Heart by Amytal.

Conclusion In a heart-lung-preparation amytal increases diastolic volume and decreases useful outflow.

Survival Time of Pregnant and Nonpregnant Rats after Bilateral Nephrectomy.

Conclusions In this series we find no statistically significant difference between survival time of pregnant and nonpregnant rats after bilateral nephrectomy in these groups of animals. These observations, therefore, lend no support to the concept that pregnancy is a burden on the kidneys. Even if the observed differences of survival time of 7 hours are in fact not due to chance, their magnitude is very small.

Activation of Pitressin by Acetic Acid.

Summary Pitressin when boiled with acetic acid becomes more potent as shown by subcutaneous antidiuretic assay and intravenous pressor assay. These effects are not due to boiling, concentration, acidity, or the presence of acetate ions. The significance of these findings in connection with the preparation of acetic acid extracts of tissues for pitressin assay is discussed.