Experimental Renal Hypertension Research Articles

CONFERENCE on the role of the renal pressor system in maintenance of experimental renal hypertension.

The hypothetical presence of increased circulating renin or hypertensin in chronic renal hypertension was debated; eventually it was agreed that methods were too insensitive for accurate assay. Pressor amounts of infused renin could not be detected by some methods of bioassay (Dr. Wakerlin). Hypertensinase activity in blood may destroy the end product before the assay can be performed (Dr. Blaquier). Perhaps rapid tissue removal from circulating blood may account for the inadequacy of the results (Dr. Skeggs). Previous experiments to detect these substances in circulating hypertensive blood have been indecisive (Dr. Braun-Menéndez) or only weakly positive (Drs. Goldblatt and Skeggs) and the clear-cut depressor effects of antirenin might act on a hypothetical nonpressor action of renin (Dr. Wakerlin). Dr. Helmer commented on the sustained pressor substance found in renal vein blood of hypertensive rats. Dr. Grollman believed chronic renal hypertension to be due to interference with an essential function of the kidney which in the normal animal prevents the blood pressure from rising. The failure of the blood pressure to rise when the kidneys from renal hypertensive dogs were perfused in situ by normotensive recipients was again discussed by Drs. Surtshin, Goldblatt and Grollman, and the possible fallacies involved in reasoning from such acute experiments were brought out. The nature of the stimulus to renin release was discussed again by Dr. Kolff. Non pulsatile flow was probably not a requirement (Dr. Kolff), nor was renal ischemia (Dr. Wakerlin), but some alteration in renal function seemed to be necessary (Dr. Goldblatt). Dr. Wakerlin and Dr. Rodbard advocated, respectively, the view that the primary stimulus might be the volume pulse or the transmural pressure in the renal arterial bed. An objection to renin as the cause of chronic hypertension based on tachyphylaxis experiments was raised by Dr. Findley. Dr. Goldblatt denied the presence of true tachyphylaxis and was supported by Drs. Helmer and Wakerlin. Dr. McCubbin suggested it might occur only with cruder preparations of renin, and Dr. Braun-Menéndez theorized that receptor sites might be occupied for a time after restoration of normal blood pressure, thus giving rise to a transient tachyphylaxis. Dr. Bumpus supported this explanation by reporting that a pressor response to crude angiotonin can sometimes not be maintained, while the response to pure angiotonin is persistent. Considerable discussion ensued between Drs. Goldblatt and Grollman concerning the mechanism of blood pressure reduction by removal of a single ischemic kidney. The human renal biopsy and autopsy studies suggesting the primacy of renal arteriolosclerosis in human hypertension were reviewed by Dr. Goldblatt.

CONFERENCE on neural control of the circulation in hypertension.

Dr. Conway reviewed his test for differentiating hypertensive patients into those with and without altered vascular elasticity. The discussion then turned to the role of the nervous system in hypertension. Experiments concerning the role of neural influences in initiating permanent hypertension were reviewed by Drs. McCubbin, Wakerlin, Langford, and Stamler. The Dock experiment of pithing hypertensive animals was then considered. His results seemed to indicate the importance of neural influences in maintaining experimental renal hypertension, but it was agreed that it was not justifiable to conclude from this work that renal hypertension was maintained by elevated neural tone (Drs. Braun-Menéndez, Bohr, Goldblatt, Kezdi, and Sapirstein). The conferees then examined the question of increased neurogenic arteriolar tone in human essential hypertension. The lack of evidence for increased neural tone, based on the failure of greater dilation following ganglionic blockade in the hypertensive subject was supported by Dr. Hoobler and opposed by Dr. Kirkendall. Most agreed that inferences from changes in peripheral resistance after blockade were fraught with error, due to the intrinsic elasticity of the arterioles (Dr. Beck), the predominance of venomotor blockade (Dr. McCubbin), the "break through" of buffer reflexes (Drs. McCubbin, Kezdi, Stamler), and the effects of varying types of anesthesia in animal experiments (Dr. Stamler). Finally, in reply to a question concerning ways to produce chronic, sustained, experimental, neurogenic hypertension, Dr. McCubbin mentioned the experiments of Taylor and Page, and Dr. Wakerlin concluded with a description of a technic for producing in dogs chronic neurogenic hypertension which had persisted in excess of 4 years. This consisted in applying a constricting plastic clamp to the carotid sinus area bilaterally, so as to reduce the volume pulse of the arterial branches of the sinus by two-thirds.

Evidence for Renotrophin as a Causal Factor in Renal Hypertension

Most of the methods used for the production of experimental renal hypertension involve a reduction in the amount of functional renal tissue. According to the renotrophin hypothesis, the blood pressure of animals with experimental hypertension should be reduced or normalized if the rate of production of renotrophin is reduced (hypophysectomy, thyroidectomy, low protein diet) or if the functional renal mass is increased (kidney transplant, parabiosis). Conversely, the blood pressure should rise to higher levels or hypertension develop if the rate of production of renotrophin is increased (thyroid hormones, somatotrophin, testosterone, thyrotrophin, gonadotrophin in males, protein-rich diets) or if the functional renal mass is further reduced (sensitizing actions of unilateral nephrectomy, etc.). Experimental evidence to be presented conforms with the renotrophin hypothesis and its 4 corollaries.

実験的高血圧症における血圧, 血管壊死及び腦出血に及ぼす肝障害の影響

実験的高血圧症における血圧, 血管壊死及び腦出血に及ぼす肝障害の影響

実験的腎性高血圧症に於ける血管障害の研究 : 特に動脈硬化症との関係に就て

The production of experimental renal hypertension was first reported in 1934 by H. Goldblatt. According to recent study, if the renal arteries were moderately constricted by modified Goldblatt's method, the cerebral massive haemorrhage occurred in the experimental hypertensive rabbits. However, the haemorrhages were observed not only in the brain but also in the other organs. Arteriolar fibrinoid necrosis was one of the chief histological findings of the vascular lesions in these experiments. This vascular lesion resembled the arteriolar lesions in the malignant hypertension, but it was also similar to vascular lesions which were observed in the apoplectic brain.In this report, following two series of experiments were performed in order to study the relationship between the arteriosclerosis and the fibrinoid necrosis.In the first series, Goldblatt's operations were performed in the rabbits prepared by the arteriosclerosis-producing procedures, namely the daily subcutaneous injection of 0.2 cc of a adrenaline for 3 months or the cholesterol feeding for 3 months (0.5 gr daily). In these arteriosclerotic rabbits, the cerebral massive haemorrhage and the fibrinoid necrosis following the Goldblarr's operation were less frequent than in the group not prepared by the arteriosclerosis-producing procedures. (Table 1, 2, 3.)In the second series, experimental hypertensive rabbits were divided into two groups. One group consisted of the rabbits which died acutely within a week after the Goldblatt's operation and another group consisted of the hypertensive rabbits with long survival. The vascular lesions in both groups were compared by the histological study. (Table 4). In the acute cases, the fibrinoid necrosis was observed in the smaller arterioles and many of them were so severe to affect all layers of the blood vessel. Fibrosis of the vascular wall not observed in this group. In the chronic cases, the fibrinoid necrosis was observed in larger arterioles and severe lesion was less frequently observed than in the acute cases. In some cases, fibrinoid substance appeared only in subintimal portion of the blood vessels. Fibrosis was marked in many arteriolar walls, which resembled the arteriolosclerosis in the organs of aged people. Clinical experience shows that the malignant hypertension is most frequent in 30-50 years old and rare in the aged. Pickering suggested that the organic arterial changes might protect the arteriolar necrosis and Nishimori reported that the fibrinoid necrosis never occurred in the arteriosclerotic vessels with fibrous thickening. Above-mentioned experiments supported their opinions.I think the foregoing organic arterial changes can make the fibrinoid necrosis mild and the healing process of the fibrinoid necrosis may produce a type of the arteriolosclerosis.

Adrenal glands in the development of renal hypertension in rats.

The adrenal glands of the rat do not appear to be necessary for the development of experimental renal hypertension by kidney encapsulation. Male and female rats became hypertensive when both kidneys were encapsulated with latex envelopes whether they were adrenalectomized two weeks prior to or at the time of kidney encapsulation. The type of hypertension produced in adrenalectomized rats did not differ from that of rats with intact adrenals with regard to time course of development of the elevated blood pressure (6–8 weeks), maximal elevation attained (190–220 mm Hg), polydipsia and hypertrophied hearts.

Dehydrogenase enzyme studies in experimental renal hypertension.

Summary1) The endogenous dehydrogenase enzyme activity, as measured by the tetrazolium technic, was determined in kidney, adrenal, thyroid, pituitary and heart tissue from untreated and reserpine treated hypertensive animals. Experimental renal hypertension was produced in rats by 3 different methods. 2) A reduction in endogenous dehydrogenase enzyme activity of kidney tissue was observed in hypertensive animals while the activity of cardiac muscle was increased. Treatment with reserpine resulted in a depression of the endogenous dehydrogenase enzyme activity in cardiac tissue of both hypertensive and normal animals.

Effect of experimental renal hypertension on experimental thiouracil-cholesterol atherosclerosis in dogs.

Experimental renal hypertension accelerated the onset and accentuated the severity of thiouracil-cholesterol atherosclerosis in dogs. Increased blood pressure and other hemodynamic changes appear to be responsible for these effects. Hypertension and sex were without significant effect on serum cholesterol, cholesterol: phospholipid ratio and low density lipoproteins. Sex had no significant effect on the incidence or severity of this experimental atherosclerosis, including coronary involvement.

Effect of hypertension on arterial wall electrolytes during desoxycorticosterone administration.

Administration of desoxycorticosterone and NaCl resulted in an increased sodium and potassium content of the aorta in rats becoming severely hypertensive. Equivocally hypertensive animals on this regimen showed smaller increases in sodium and a decrease in potassium. Sodium restriction prevented both hypertension and changes in arterial wall chemistry from occurring in rats receiving desoxycorticosterone. Hypertension per se may be fundamentally associated with an increased potassium and sodium content in artery, as experimental renal hypertension is characterized by a similar electrolyte alteration.

Congenital Malformation of the Renal Artery, a Cause of Hypertension

The causal relationship of renal pathology to arterial hypertension is not yet clearly defined. The classic experiments of Goldblatt (10) convincingly demonstrated that interference with the renal arterial blood flow through one or both kidneys in the experimental animal can result in sustained hypertension. Goldblatt (11, 12) presents formidable evidence to show that such experimental hypertension bears a striking similarity to essential hypertension in man and suggests that the mechanisms in the two may be identical. There is, however, a large body of opinion which is strongly opposed to this point of view. Indeed, Smith (24), Goldring (13), and Thompson and Smithwick (26) insist that, with the possible exception of pyelonephritic and pyonephrotic atrophy, urologic disease does not increase the incidence of hypertension, nor is renal disease more common in the hypertensive than in the normotensive population. Be that as it may, there is general agreement that there are at least certain forms of renal disease which definitely represent the exact human counterpart of the experimental renal hypertension of Goldblatt. Such cases are those in which, for one reason or another, there is a marked reduction, but not a complete suppression, of the arterial blood flow through one or both kidneys. While the actual mechanism is not definitely understood, it is generally assumed that a relatively ischemic kidney elaborates a pressor substance which acts as a humoral hypertensive agent. The occasional cases of unilateral renal disease in which removal of the diseased kidney alleviates or cures the hypertensive state, lend support to this theory. These cases comprise a very small but nevertheless an important segment of all cases of hypertension in man. The most obvious instances in this category are the lesions which reduce the renal blood flow directly by mechanical narrowing of the lumen of the main renal artery. Such mechanical narrowing may be caused by thrombosis, arteriosclerotic plaques, aneurysm, neoplasm, or congenital anomaly. Congenital malformation of the renal artery, producing hypertension by the Goldblatt mechanism, is undoubtedly a rare entity. Yet, it probably occurs more often than it is actually found or even suspected. Careful search of the literature reveals a remarkable paucity of reported examples, and none has appeared, as far as we could discover, in the roentgenologic literature. In 1954, Howard et al. (17), reporting on 6 hypertensive patients with unilateral renal disease, described a case (Case 3) of a thirty-nine-year-old man from whom a non-functioning left kidney was removed. Pathologic examination of the specimen disclosed that the main renal artery was absent and in its place several small arteries entered the hilus of the kidney.

The electrolytes of arterial wall in experimental renal hypertension.

In rats with renal hypertension, smooth muscle cells in the wall of the aorta appear to have more water, sodium, potassium, magnesium and phosphorus per unit of cell solids than similar cells in normotensive rats. When the blood pressure of a few hypertensive rats dropped to normal as a result of a low sodium diet, the potassium and phosphorus in the arterial cells also appeared to decrease to normal levels. These studies give indications of the compositional changes in arterial smooth muscle cells that are associated with renal hypertension.

Mechanism of early and chronic experimental renal hypertension as tested by CCK-179.

The effects on blood pressure and renal clearances of a combination of dihydrogenated ergot alkaloids, CCK-179, were studied in normal dogs and dogs with experimental renal (Goldblatt) hypertension. The drug was observed to have a maximal effect at 0.012 mg/kg, about one twelfth to one sixteenth the dose recommended in the literature. In normal dogs the drug causes a slight fall in blood pressure, a moderate decrease in glomerular filtration rate (creatinine clearance) and a pronounced decrease in renal plasma flow (PAH clearance), hemodynamic effects resembling those seen in man. After repeated administration of the drug, the renal effects are of greater magnitude in these dogs. In hypertensive dogs, CCK-179 causes blood pressure to approach normal levels. In the early weeks of hypertension, the renal effects of the drug are similar to those seen in normals but as hypertension increases in duration up to 55 weeks, the decreases in filtration rate and plasma flow become progressively smaller. This could indicate that in chronic experimental renal hypertension the high peripheral resistance is maintained at least in part by increased activity of the sympathetic nervous system rather than by the action of the components of the renal humoral pressor system.

The reported inhibition of DCA-salt hypertension by antihistaminic drugs: effects of sandostene, phenergan and chlorpromazine.

TREATMENT of uninephrectomized rats with desoxycorticosterone acetate (DCA) and salt results in renal, splanchnic, myocardial and cerebral vascular lesions identical with those of experimental renal hypertension and similar in many respects to the lesions of hypertensive disease in human beings (Selye, 1942; Masson et al., 1949). The mechanism of formation of these lesions is unknown, except that arterial hypertension seems to be a contributory factor. That altered vascular permeability, with trapping in the vessel walls of a protein component of plasma might play a role in hyalinization and fibrinoid change in the arterioles is suggested in part by the microscopic appearance of some of these lesions. This possibility receives further support from the finding that desoxycorticosterone, in the presence of excess Na ion, increases permeability of vessels in preparations of isolated limbs (Tripod and Meier, 1952). The importance of increased permeability in this connection seems to have been confirmed by the...

Renin and antirenin in treatment of long term experimental renal hypertension in the dog.

Summary and Conclusions1. Courses of intramuscular injections of semipurified hog renin from cortex administered to dogs with experimental renal hypertensions of 4 or more years duration produced a significant reduction in blood pressure in those dogs which developed antirenin but not to normotension as previously found in dogs with chronic renal hypertension of 6 to 37 months duration. The 2 dogs which did not develop antirenin showed a maintained chronic pressor effect. 2. Passive immunization with homologous antirenin to hog renin produced a reduction in blood pressure to normotension or near normotension in dogs with experimental renal hypertensions of more than 7 years duration. 3. The mechanism of the decreased response to hog renin therapy in long term experimental renal hypertension in the dog is unknown. The results with passive immunization suggest that a lessened pathogenetic role for renin is not involved nor is progressive arteriolosclerosis. Possibly compensatory hypertensive mechanisms are ...

Persistence of experimental renal hypertension after total nephrectomy in dogs.

Persistence of experimental renal hypertension after total nephrectomy in dogs.

Sodium tolerance in experimental hypertension.

A sodium tolerance test was applied to rats subjected to three diverse procedures for the production of experimental renal and hormonal hypertension. Sodium tolerance was impaired in all three types of hypertension to the extent that an accelerated excretion of the imposed sodium load occurred, although there was no change in the plasma sodium level. The disturbance was proportional to the height of the blood pressure but occurred even in those treated rats which remained normotensive.

Effect of pitressin in experimental renal hypertension in the rat.

ArticleEffect of Pitressin in Experimental Renal Hypertension in the RatSydney M. Friedman, Constance L. Friedman, and Miyoshi NakashimaSydney M. FriedmanFrom the Department of Anatomy, University of British Columbia, Vancouver, Canada, Constance L. FriedmanFrom the Department of Anatomy, University of British Columbia, Vancouver, Canada, and Miyoshi NakashimaFrom the Department of Anatomy, University of British Columbia, Vancouver, CanadaPublished Online:28 Feb 1955https://doi.org/10.1152/ajplegacy.1955.180.3.469MoreSectionsPDF (993 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByDie Bedeutung der experimentellen Analyse f�r die therapeutische Anwendung blutdrucksenkender PharmakaKlinische Wochenschrift, Vol. 33, No. 47-48 More from this issue > Volume 180Issue 3February 1955Pages 469-474 Copyright & PermissionsCopyright © 1955 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1955.180.3.469PubMed14376523History Received 17 August 1954 Published online 28 February 1955 Published in print 28 February 1955 Metrics

Effect of mean circulatory filling pressure and other peripheral circulatory factors on cardiac output.

I P ONE studies curves which depict the relationship of cardiac output to mean right atria1 pressure (one of the forms of Starling’s curves), it is obvious that, within the normal range of function of the heart, cardiac output can change tremendously while the right atria1 pressure changes only slightly. This fact led to the early belief that it is not the function of the heart itself which controls cardiac output but instead that cardiac output is controlled by the various factors in the peripheral circulatory system which regulate the return of blood to the heart. Though it is not entirely true that cardiac output is independent of the function of the heart (I), nevertheless, it is hoped to emphasize in the present paper the special importance of the peripheral circulatory factors which affect venous return. In order to do this, a mathematical circuit analysis of the closed circuit circulatory system has been made. This circuit analysis has been specifically simplified so that the factors derived would be amenable to experimental test. Two of the factors which have proved to be of importance, as shown both by this circuit analysis and by experimental data, are a) ‘capacitance’ and b) ‘mean circulatory filling pressure.’ As used in these studies the term capacitance means dV/dP or, in other words, the change in volume of a particular part of the circulatory system with each unit change in pressure. This term has been used in the present paper because there is at present no term in common usage in hydrodynamics which means dV/dP. This is different from the term ‘distensibility’ which is commonly used to mean dV/dP + V. The term mean circulatory filling pressure (MCFP) has been defined previously (2), and it means ,__-

EXPERIMENTAL AND CLINICAL STUDIES ON HYPERTENSION

I. Relationship between RBF and Blood Pressure in Experimental Renal Hypertension:In order to clarify the significance of renal ischemia in experimental renal hypertension, 11 dogs subjected to the Goldblatt's operation were followed for about 6 months, during which blood pressure and RBF were measured simultaneously, and then the following conclusions were obtained:1. To produce the sustained elevation of blood pressure in dogs subjected to the Goldblatt's operation, it is necessary PBF to be reduced less than at least 80% compared to the preoperative levels.2. In the course of time, there was a certain tendency for RBF to approach the initial level, but the elevated blood pressure continued approximately its high levels.II. Demonstration of Pressor Substances from Renal Venous Blood in Essential Hypertension.To Know whether or not pressor substances are present in the blood of the patient of essential hypertension is of the utmost importance. A series of experiments was undertaken, therefore, in an attempt to demonstrate their presence, and the following results were obtained:1. In the extracts from 8 of 19 hypertensive patients, pressor effects were found. Their RBF showed reduction under 50% compared to normal ones.2. In the extracts from 5 normal individuals these pressor effects were absent.III. In conclusion, although depression of RBF under certain level is necessary, for the production of experimental renal hypertension the way in which essential hypertension is initiated in man may not involve the kidney. It is suggested that some factors other than the kidney probably participate in early essential hypertension and late stage of experimental renal hypertension. Following the reduction of RBF in essential hypertension, however, the ischemic kidneys liberate pressor substances into the circulation, and the kidney may play a role as one mediator of hypertension.

Effect of diet on experimental hypertension and on the development of polyarteritis nodosa in rats.

Rats with experimental renal hypertension were fed various diets differing in sodium and protein content. Marked prolongation of life was achieved by rice diet. Polyarteritis nodosa developed, as a result of the experimental procedures, in 23.5 per cent of the animals. Its incidence was closely correlated to sodium ingestion: 4 per cent in rats on low sodium intake, 36 per cent in rats on normal or slightly higher sodium intake. Protein intake showed no effect on incidence of polyarteritis but distinct effect on survival time. Except for one rat where a sarcoma destroyed almost all kidney tissue, no animal on rice diet developed polyarteritis nodosa.