Renal Artery Constriction Research Articles

Recent advances in hypertension

The possible relationship between the renal mechanism of volume control and blood pressure regulation is discussed. Expansion of the extracellular fluid (ECF) and plasma volumes was demonstrated following renal artery constriction in the rat; after about one month ECF volume returned to normal although hypertension persisted. Measurements of cardiac output in the unanesthetized rat by an implanted electromagnetic flowmeter showed an initial rise in cardiac output after renal artery constriction, returning to normal in 10 to 15 days. A homeostatic hypothesis for the production of renal hypertension is put forward in which changes in ECF volume, capacity vessel tone and myocardial contractility participate in the development of hypertension by elevating cardiac output. Autoregulation of peripheral flow then occurs and the consequent restoration of blood pressure at a renal pressure receptor results in return to normal of cardiac output by negative feedback. Thus in chronic hypertension the high peripheral resistance is maintained by autoregulation.

Major segmental renal arterial constriction: an experimental study in the dog.

SUPERNUMERARY renal arteries are found in approximately 33 per cent of kidneys examined at necropsy (8). Renal artery stenosis is also relatively common in both normotensive and hypertensive patients over fifty years of age (2, 5, 7). This would suggest that narrowing of a supernumerary renal artery is probably not rare. The purpose of this communication is to discuss the radiologic findings resulting from functionally significant constriction of a major segmental renal artery. Methods An experimental study of hypertension and renal artery stenosis (main single renal artery as well as major segmental arteries) was undertaken in mongrel dogs weighing 12–15 kg. After a twelve-hour fast, preliminary sedation with intramuscular meperidine hydrochloride was followed by intratracheal intubation and intravenous sodium pentobarbital anesthesia (30 mg/ kg). According to Blatteis and Horvath, this type of anesthesia produces no significant alterations in renal function (1). Isotopic renography, renal scanning, and ...

DIVERSION OF RENAL VENOUS BLOOD INTO THE LIVER: EFFECTS ON EXPERIMENTAL HYPERTENSION IN DOGS.

THE LIVER is well known for its ability to metabolize endogenous substances. Its possible role in modulating the pressor substance released by the ischemic kidney was first investigated by Child and Glenn1in 1938. These authors concluded that the diversion of venous blood from the ischemic kidneys into the liver did not effect the elevated blood pressure. In the same year Levy and Blalock2reported on the ineffectiveness of such diversion in preventing the development of hypertension when the artery to the only remaining kidney was later constricted. This aspect of experimental renal hypertension remained dormant until 1962 when Aoki3reported on the effectiveness of renalportal venous shunt in restoring normotensive condition in the hypertensive dog and preventing the development of hypertension due to subsequent renal-artery constriction. He related this to the detoxifying ability of the liver. In an attempt to find an explanation for these contradictory

LIMITED HYPERTENSIVE EFFECT OF INFUSION OF ANGIOTENSIN.

Though single injections of angiotensin cause extreme rise in arterial pressure, infusion fails to elevate pressure to the degree usually found in experimental renal hypertension. The maximal pressure level obtainable by infusing angiotensin into anesthetized dogs was approximately the same in different dogs and was independent of the initial pressure. The vagus nerves did not importantly influence the "ceiling" response but if arterial pressure was then elevated by carotid occlusion the ceiling was raised. The combination of renal artery constriction and infusion of angiotensin failed to give a higher ceiling than angiotensin alone. In dogs with chronic renal hypertension the ceiling was higher than in normal dogs, presumably because of an upward shift in the range of response of cardiovascular reflexes. The results support the view that compensatory cardiovascular reflexes and tachyphylaxis to large amounts of infused angiotensin suppress the response and that these factors are much less effective in limiting response to quick injection.

RELATION OF SUPERIOR-MESENTERIC-ARTERY OBSTRUCTION TO RENAL HYPERTENSION: A REVIEW OF 56 CASES.

BLALOCK et al.1 demonstrated in dogs that unilateral renal-artery constriction resulted in a greater rise in blood pressure if the superior mesenteric artery was also previously constricted. Furthermore, in their animals the hypertension was sustained for at least one year, whereas Goldblatt and his associates2 had found that hypertension produced by constriction of only one renal artery was sustained for less than six weeks unless contralateral nephrectomy was performed. Constriction of the superior mesenteric artery alone had no effect on blood pressure.3 These experiments showed that superior-mesenteric-artery insufficiency enhanced the hypertension of renal-artery insufficiency by an unknown mechanism. Pertinent case . . .

Hemodynamic Changes in Trained Dogs During Experimental Renal Hypertension

The hemodynamic events, during onset of experimental renal hypertension, and during its progression to the chronic state, were recorded in 19 trained quiet dogs for 20 to 30 minutes daily for four to forty-two days. This was made possible by implanting a flow probe around the root of the aorta, and a catheter in the aortic arch for connection to an external pressure gauge. Continuous graphic recordings of blood pressure, cardiac output, stroke volume, heart rate, and peripheral resistance were made daily during a period of training to obtain control values, and after hypertension was initiated by partial occlusion of a renal artery and unilateral nephrectomy. The average mean arterial pressure in 34 unanesthetized dogs in this study was 85 mm Hg (range, 68 to 116 mm Hg). This is about 30% below values previously reported by others in unanesthetized dogs. These low pressures were ascribed to lack of restraint, to training, and to the natural posture of the dogs. At onset of hypertension a sharp rise in arterial pressure was accompanied by a decrease of cardiac output and heart rate, and by a large abrupt increase of peripheral resistance. After one to four days, the continued rise of arterial pressure was associated with return of cardiac output and heart rate toward normal. Peripheral resistance eventually stabilized at a level above that of the initial large rise. A chronic state of hypertension was reached by ten to twenty days after the initial rise of pressure. At this time cardiac output and heart rate were restored to normal, while peripheral resistance remained elevated. Studies lasting for as long as forty-two days did not show further changes. If the renal arterial constriction was severe, a third, "malignant" phase ensued with extreme elevation of diastolic pressure, reduction of cardiac output, and greatly increased peripheral resistance. This terminated in uremic death after a few days.

HEMODYNAMIC ASPECTS OF PROLONGED INFUSION OF ANGIOTENSIN INTO UNANESTHETIZED DOGS.

Arterial pressure, cardiac output, stroke volume, heart rate, and peripheral resistance have been recorded daily in eight trained, healthy dogs with implanted aortic flow probes and aortic catheters. After suitable control periods angiotensin II was infused for periods of from 2 to 29 days. The effects observed were considered under four categories: 1) The immediate effects consisted of rise of arterial pressure, decrease of cardiac output and heart rate, rise of peripheral resistance and increased pulse pressure. Within five days all values tended to return to control levels unless the infusion rate of angiotensin was increased. 2) A chronic phase followed and, during this period, cardiac output was normal while arterial pressure and peripheral resistance were elevated. 3) After infusions were stopped pressure and peripheral resistance rapidly declined to be low normal, while cardiac output and heart rate rose to above normal. 4) A transient "malignant" phase was elicited by very large increases in the rate of angiotensin infusion, during which cardiac output and stroke volume were diminished while arterial pressure and peripheral resistance were increased greatly. The hemodynamic changes resulting from prolonged angiotensin infusion were similar in some respects to those found by us during the onset of hypertension due to renal artery constriction in dogs. They differed, however, in that doses of angiotensin, which were great enough to induce arterial pressure elevations similar to those of chronic experimental renal hypertension, reduced stroke volume, and these higher pressures could not be maintained for more than a few days. Hypertension did not persist after discontinuing angiotensin even after 28 days of almost continuous infusion. There was a distinct tendency for the pressor response to diminish with passage of time; more angiotensin was required to maintain similar elevations of arterial pressure.

EFFECT OF ALDOSTERONE ON JUXTAGLOMERULAR INDEX AND ZONA GLOMERULOSA OF NORMOTENSIVE AND HYPERTENSIVE RATS.

SummaryInjections of aldosterone produced moderate, but significant, elevation of blood pressure in normotensive rats. A comparable elevation of blood pressure was noted in rats with existing renal hypertension produced by unilateral renal artery constriction. JGI and ZGI were decreased in kidneys and adrenals from both aldosterone-treated groups. These findings are interpreted to indicate the indirect role of aldosterone in regulating renin production. Aldosterone failed to influence the vascular lesions of renal hypertension.

STUDIES OF PATIENTS WITH RENAL HYPERTENSION UNDERGOING VASCULAR SURGERY.

IT is now well established that renal ischemia, unilateral or bilateral, brought about by any pathologic process, may cause hypertension in man,1 , 2 as it does in animals.3 As in animals, if the renal ischemia is unilateral, and the contralateral kidney is normal, or at least not ischemic, excision of the ischemic kidney cures the hypertension.4 5 6 No fall in the blood pressure was observed when the more diseased kidney was removed from a patient with bilateral nephrosclerosis.7 Since the ischemia in the laboratory animal is due to constriction of the main renal artery by a metal clamp and not to organic, . . .

Renal alterations in dogs during renal arterial constriction, hemorrhagic hypotension and osmotic diuresis

Renal alterations in dogs during renal arterial constriction, hemorrhagic hypotension and osmotic diuresis

Effects of chronic electrical stimulation of diencephalon on aortas in rabbits.

1) Effects of chronic electrical simulation of the diencephalon on the aortic wall were studied in rabbits with or without unilateral renal artery constriction.2) A kind of aortic sclerosis was observed in high incidence in animals with the diencephalic stimulation and the renal artery clamping in combination.(3) Histological examination of the aorta revealed that lesions were mainly located in the medial layer, in which degeneration of smooth muscle cells and discurling, elongation and fragmentation of elastic fibers were observed.(4) Small doses of epinephrine were repeatedly injected to rabbits and changes of the aortic wall were examined. The changes were more cospicuous in animals with unilateral renal artery constriction and were found to be histologically similar to that observed in above mentioned animals.(5) It was assumed that chronic diencephalic stimulation or repeated injections of epinephrine and the presence of an ischemic kidney might act synergetically to induce aortic sclerosis in rabbits.

ASSESSMENT OF CURABLE RENOVASCULAR HYPERTENSION BY RADIOGRAPHIC TECHNICS.

During the past ten years, there has been an increasing interest in the radiographic diagnosis of renovascular hypertension. Many patients suffering from severe hypertension have been cured by surgery. The cure rate, which varies somewhat from institution to institution, definitely seems to justify surgical repair of stenotic renal artery lesions in a carefully selected group of patients. Unfortunately, some who are operated upon for renal artery stenosis show insignificant or no alleviation of the hypertension. It is the purpose of this presentation to discuss two radiographic technics—aortography combined with pressure measurements and the urea washout test—both of which assess the physiologic alterations associated with curable renovascular hypertension, thus being helpful in selecting those patients who will benefit from surgery. Renal disease was first associated with fullness of the pulse and hypertrophy of the heart by Richard Bright in 1827 (1, 2), but exact blood pressure determinations were possible only after Riva-Rocci described the sphygmomanometer in 1896 (3). Because malignant hypertension was difficult to produce in the experimental animal, little progress was made until 1934 when Goldblatt (4) showed that a constricting clamp applied to one renal artery in the dog caused a moderate but transient rise in blood pressure. Additional partial constriction of the contralateral renal artery by a similar clamp, however, resulted in persistent marked hypertension. This new concept was enthusiastically applied to human hypertension. In the years to follow, many nephrectomies were carried out, but a failure rate of 75 per cent resulted, as summarized by Smith in 1948 (5). This poor therapeutic result was chiefly due to inadequate technics for the selection of patients for surgery, since angiography was not commonly available at that time. With the description of the characteristic basic physiologic alterations in curable renovascular hypertension by Howard (6) in 1953 and the advances in radiology, the surgical cure rate has improved considerably during the past few years. Since these patients can presently be handled effectively by medical management also, the selection of those who will be cured by surgery becomes of increasingly practical importance. A wide variety of unilateral renal lesions may cause curable malignant hypertension. By far the most common and most important is stenosis of the main renal artery (Fig. 1, a), which may be due to atherosclerotic or congenital narrowing, fibromuscular dysplasia, and, rarely, to extrinsic compression as from a band or tumor. Stenosis of an accessory renal artery and renal branch stenosis are less common (Fig. 1, b and c). The presence of segmental renal arteries without partial obstruction is not likely to cause renovascular hypertension.

DIFFERENCES IN LEVELS OF CIRCULATING VASOPRESSOR MATERIALS IN DOGS WITH ACUTE AND CHRONIC RENAL HYPERTENSION.

SummarySmall amounts of plasma from dogs with acute renal hypertension were shown to contain easily detectable amounts of a vasopressor substance for approximately the first 2 weeks after renal artery constriction. This is consistent with the view that a humoral mechanism plays a role in the origin of the high blood pressure. With our technique the vasopressor material tended to disappear from the blood between 1 and 3 weeks after renal artery clamping and thereafter all assays of plasma for vasopressor activity were negative. Thus, in the dog as in the rat, and for reasons not clear, the acute and chronic stages of experimental renal hypertension differ sharply in respect to recovery of circulating pressor substance. While this finding does not necessarily exclude a humoral system from participating in the pathogenesis of chronic renal hypertension, it indicates that the level per se of circulating vasopressor material is not the critical factor in sustaining the high blood pressure in this stage.

PAPER CHROMATOGRAPHIC IDENTIFICATION OF ANGIOTENSINS.

The separation of angiotensin I and angiotensin II by paper chromatography using an acid NaCl solution is described. When the pressor material recovered from the blood of dogs infused with renin was analyzed by this method, significant quantities of angiotensin I as well as angiotensin II were found in those infused at rates above 1 Goldblatt U/min. At infusion rates below 1 U/min, only angiotensin II was present. In each of six dogs with malignant experimental renal hypertension, significant increases in circulating pressor material were found 48 hr or more after renal artery constriction. Analysis of the material recovered from the blood of five of these dogs revealed only angiotensin II in four instances, and a mixture of angiotensin I and II in one instance.

A RENAL FACTOR IN HYPERTENSION DUE TO COARCTATION OF THE AORTA.

RENAL disease is instrumental in the generation or maintenance of some forms of systemic arterial hypertension. The experimental production of systolic hypertension by renal artery constriction, by suprarenal coarctation of the aorta, or by establishment of fibrocollagenous perinephritis in animals suggests a renal factor in such hypertension involving an alteration of renal blood flow or renal ischemia per se.1 2 3 4 The clinical counterpart of this assumption stems from the recorded success of reconstructive procedures reversing hypertension in patients with renal-artery stenosis.5 , 6 The correction of hypertension by removal of an ischemic kidney, the physiochemical function of which is measurably altered, further fosters . . .

Effects of Cortexone and Salt on Renin Content, Juxtaglomerular Index and Renal Hypertension in Rabbits

SummaryIn unilaterally nephrectomized rabbits, cortexone and salt administration reduces renin content and the juxtaglomerular granulation index of the kidney and does not provoke hypertension. Renal artery clamping induces a rise in blood pressure without causing changes in renin content nor JGI, which remain normal. Combination of these 2 experimental procedures is followed by hypertension and a decrease in renin content and JGI. The width of the adrenal zona glomerulosa is reduced under the influence of cortexone and salt, and remains unaffected by renal artery constriction. In the rabbit, therefore, mineralocorticoids seem to play no major role in induction of renal hypertension. Neither does renin appear as a necessary agent in the mechanism responsible for the development of renal hypertension.

ON CHANGES IN BLOOD VESSEL WALL ELECTROLYTES AND THE ADRENAL CORTEX IN EXPERIMENTAL HYPERTENSION

Reactivity to pressor substances increases in hypertensive subjects, while it decreases in patients suffering from secondary aldosteronism with edema. It is generally recognized that the contraction of vascular smooth muscle is influenced by the concentration of electrolytes in extracellular and intracellular fluid. Comparisons were made of the electrolyte content of the various tissues in hypertensive rats and those in rats with edema. The adrenal cortices of hypertensive rats caused by the constriction of the unilateral renal artery were studied histologically. Discussions were made of the role that aldosterone plays in renal hypertension of vascular origin. Materials and Methods Male Wister rats were divided into eleven groups and received each treatment as follows. A) control, B) the clipping of the unilateral renal artery, C) administration of triamterene to the hypertensive rats caused by the clipping of the renal artery, D) administration of aldosterone, E) administration of corticosterone, F) administration of aldosterone and corticosterone, G) administration of DOCA, H) administration of DOCA and NaCl, I) administration of aminonucleoside, J) administration of aminonucleoside and triamterene, K) administration of carbon tetrachloride. Blood pressure was determined, and the sodium and potassium content of the aorta, psoas muscle and heart muscle were measured. The adrenal glands of the renal hypertensive rats were removed, stained with hematoxylin-eosin or scarlet-red and submitted to histological examination. Results 1) Blood pressure and sodium and potassium content of the aorta. Blood pressure became elevated one week after the clipping of the renal artery The sodium content of the aorta increased slightly, and the potassium content increased significantly in rats in which hypertension was noted two weeks after the clipping. Both sodium and Potassium content increased significantly ten weeks after the clipping. Blood pressure in renal hypertensive rats failed to fall and the sodium and potassium content remained elevated despite the administration of triamterene. The administration of DOCA and NaCl induced elevation of blood pressure. In this group, both sodium and potassium content of the aorta increased significantly. In other groups to which the steroids of the adrenal cortex were administered, blood pressure was not elevated. In some groups of these normotensive rats, the sodium content of the aorta increased but the potassium content did not increase. The sodium content increased, while the potassium content decreased in rats with nephrosis caused by aminonucleoside and in rats with cirrhosis of the liver caused by carbon tetrachloride.

EFFECT OF CHRONIC ELECTRICAL STIMULATION OF DIENCEPHALON ON BLOOD PRESSURE IN RABBITS.

Effect of chronic electrical stimulation of diencephalon on blood pressure was studied in rabbits with and without unilateral renal artery constriction which has been considered to be an insufficient condition to produce permanent hypertension in rabbits. In only 2 of 9 intact rabbits with the stimulation alone, gradual elevation of blood pressure was recognized beginning about 30 days after initiation of the stimulation and reaching levels of 40mm.Hg above their control ones in 90 days. In contrast, 9 of 12 animals in which unilateral renal artery clamping and the stimulation were performed, showed maintenance of more significant elevation of blood pressure, and 3 of the hypertensive rabbits died from cerebral hemorrhage during the period of stimulation. In the hypertensive animals given the stimulation, dorsal hypothalamic area was proved to be frequently the site of stimulation.It is considered that sympathetic stimuli and renal pressor mechanism may act synergetically to produce hypertension in rabbits.

RENAL ARTERY RESPONSE OF EPINEPHRINE.

Conclusions(1) Pharmacologic doses of intravenous epinephrine in dogs caused a significant decrease in the vascular phase and a slower ascent to peak concentration of the I131 radiorenogram. These changes are essentially the same as noted to occur in humans who suffered with acute apprehension during the test procedure. (2) These same doses of epinephrine caused an intense constriction of the renal arteries proximal to or at the first major bifurcation as visualized with angiography and cineradiography. In one-fourth of the dogs the renal artery constriction was noted to occur within one to one and one-half centimeters of their aortic origin. The renal arteries proximal to the constricted zone were dilated.

Effect of Renal Hypertension in Sodium Deficient Rats on Juxtaglomerular Index and Zona Glomerulosa.

SummaryComparable degrees of renal hypertension were induced in sodium deficient rats and those receiving normal sodium intake following unilateral renal artery constriction. Sodium depletion had no effect on blood pressure of rats with established renal hypertension and similarly sodium supplement did not affect the renal hypertension of sodium deficient animals. JGI of untouched kidneys and width of zona glomerulosa of adrenal cortices in sodium-deficient hypertensive rats were greater than in those receiving sodium but less than those of sodium deficient controls. This suggests that changes in JGI of untouched kidneys of hypertensive rats primarily reflect the sodium state of the animals and to a less extent the effect of blood pressure per se.