Experimental Renal Hypertension In Dogs Research Articles

Role of endogenous endothelin-1 in experimental renal hypertension in dogs.

Endothelin-1, a vasoconstrictive peptide released by endothelium, may be involved in the pathophysiology of hypertension. The goal of the present study was to evaluate the role of endogenous endothelin-1 in renal hypertension in dogs. The model of hypertension consisted of silk tissue wrapping of the left kidney, which produced hypertension associated with perinephritis after 6 to 8 weeks. Thirty-two anesthetized open chest dogs were studied randomly: 8 dogs with perinephritic hypertension received the nonpeptidic ETA-ETB receptor antagonist bosentan (group 1); 8 other hypertensive dogs received the vehicle solution (group 2); 8 healthy dogs received bosentan (group 3); and 8 healthy dogs received the vehicle solution (group 4). Bosentan was injected as an intravenous bolus (3 mg/kg) followed by a 1-hour infusion at a rate of 7 mg.kg-1.h-1. In hypertensive dogs, bosentan produced a similar decrease (P = .0001) of both left ventricular systolic and mean aortic pressures, which averaged 38 mm Hg (-22% and -24%, respectively). These parameters remained unchanged with the vehicle solution. Left ventricular end-diastolic and left atrial pressures also declined significantly with bosentan (P = .0005 and P < .05, respectively). Left ventricular lengths tended to decrease. The other cardiovascular parameters (heart rate, peak [+]dP/dt, time constant of relaxation, and coronary vascular resistance) did not change significantly. In healthy dogs, bosentan decreased mean aortic pressure by 19 mm Hg (P = .004). Vehicle solution had no effect. Plasma endothelin-1 levels, similar under basal conditions in healthy and hypertensive dogs, increased 30-fold with bosentan (P = .0001). Specific endothelin-1 receptor antagonism markedly lowers blood pressure in experimental hypertension but is less effective on blood pressure of healthy animals. This suggests that endothelin-1 plays a role in the pathophysiology of hypertension but contributes to a lesser extent to the maintenance of normal blood pressure. This role of endothelin-1 is unrelated to its plasma levels. The increase of plasma endothelin-1 with bosentan, due either to a displacement of endothelin-1 from its receptor or to a feedback mechanism, does not prevent this blood pressure reduction.

Mesenteric hemodynamics in early experimental renal hypertension in dogs.

To investigate mesenteric hemodynamics in early perinephritic hypertension, we measured blood flows and intravascular pressures in innvervated, collateral-free, naturally perfused loops of ileum in 50 male mongrel dogs anesthetized with sodium pentobarbital. In addition, we studied venous pressure-volume relationships in temporarily occluded segments of mesenteric veins in vivo and in excised segments of mesenteric veins in vitro. In 10 dogs (group H-1), one kidney was wrapped in silk 11 days before study; in 15 other dogs (group H-2), one kidney was wrapped 4 weeks before study and the other was removed 2 weeks before study. Twenty-five additional dogs were prepared as normotensive controls: in 10 one kidney was sham-wrapped (group C-1), and in 15 one kidney was sham-wrapped and the other was removed (group C-2). A significant rise in mean arterial blood pressure occurred in groups H-1 and H-2. Compared to controls, (1) ileal blood flow in the hypertensive dogs (H-1 plus H-2) was increased by 17% (P smaller than 0.05), (2) calculated ileal vascular resistances (total and segmental) were unchanged (P smaller than 0.05), and (3) in vivo and in vitro mesenteric vein pressure-volume curves of H-2 (but not of H-1) hypertensive dogs were shifted in the direction of the pressure axis (P smaller than 0.05). These data suggest that in the early stages of perinephritic hypertension in dogs (1) ileal blood flow is increased. (2) ileal vascular resistance is not elevated, and (3) mesenteric venous compliance is reduced. Analysis of the venous pressure-volume curves suggests that the decreased venous compliance is attributable to factors other than smooth muscle contraction.

Hemodynamics of early experimental renal hypertension in dogs. Normal limb blood flow, elevated limb vascular resistance, and decreased venous compliance.

To investigate the hemodynamics of early experimental renal hypertension, skin and muscle blood flows and intravascular pressures were measured in the isolated, innervated, naturally perfused forelimbs of 44 male mongrel dogs under pentobarbital (35 mg/kg) anesthesia. In addition, venous pressure-volume relationships were studied in temporarily isolated segments of femoral and jugular veins. In 10 dogs (group H-1) one kidney was wrapped in silk 8 days before study; in 12 (H-2) one kidney was wrapped 4 weeks, and a contralateral nephrectomy was done 2 weeks, before study; 22 were prepared as appropriate normotensive controls. A significant rise in mean arterial pressure occurred in groups H-1 and H-2. Compared to corresponding control groups, (1) muscle and skin blood flows in both hypertensive groups were unchanged ( P &gt;0.1); (2) muscle and skin resistances/100 g limb weight were increased in group H-2 ( P &lt;0.05); and (3) femoral venous pressure-volume curves were shifted toward the pressure axis ( P &lt;0.02). These data suggest that in the early stages of experimental renal hypertension in dogs: (1) blood flow in skin and skeletal muscle is not increased; (2) arteriolar resistance is elevated in skin and skeletal muscle; and (3) reduced venous compliance may be present.

Increased cardiac output as a contributory factor in experimental renal hypertension in dogs.

It has been suggested, but not established, that renal hypertension is initiated by increase incardiac output. Recent refinements in electromagnetic flowmeter technology allowed a critical reevaluation of this possibility. Flowmeters were implanted around dogs' ascending aortas and arterial catheters inserted; measurements were made daily before and after production of hypertension by the cellophane perinephritis method. Eight to 15 days after wrapping one kidney in cellophane, with the opposite kidney untouched, group averages for both stroke volume and cardiac output rose significantly (P &lt; 0.005) though there was no change in arterial pressure. Both heart rate and peripheral resistance decreased slightly. Following these measurements, the contralateral normal kidney was removed and measurements were recommenced 24 hours later. After 4 to 7 days, mean arterial pressure rose progressively in all dogs, reaching a plateau 77 ± 8 (SE) mm Hg above control after 14 to 25 days. Hypertension was associated initially with further rise in both stroke volume and cardiac output, and peripheral resistance now became elevated. Four weeks after nephrectomy, peripheral resistance progressively became the predominant cause of elevated pressure while cardiac output returned toward control values. Absence of change in plasma volume and increase in mean circulatory pressure measured in a separate series of 7 dogs suggest that the initial increase in cardiac output preceding rise in pressure was due to enhanced venous return consequent to constriction of capacitance vessels. We conclude that increased cardiac output probably has a contributory role in the development of renal hypertension.

Changes in Sodium Balance and Hemodynamics during Development of Experimental Renal Hypertension in Dogs

After unilateral nephrectomy and application of a Goldblatt clamp to the remaining renal artery, there was sodium retention of approximately 123 mEq in 15 days. At this time, blood pressure increased from 95 to 142 mm Hg without demonstrable changes in plasma volume or cardiac output. When the accumulation of sodium was prevented and a negative balance induced by a low sodium diet and a single dose of a diuretic agent postoperatively, the blood pressure increased from 102 to 139 mm Hg, but it increased further, to 155 mm Hg, after a normal sodium diet had been restored and there had been a gain of 189 mEq of sodium above control. The accumulation of sodium after application of the Goldblatt clamp does not appear to be necessary for the emergence of hypertension, but it does appear to play some part in determining the magnitude of the rise in pressure.

Neurogenic Component of Chronic Renal Hypertension

Infusion of angiotensin or renin in small quantities affects the sympathetic nervous system so that responses are increased to either drugs or reflexes that cause release of norepinephrine at nerve endings. Response to injected norepinephrine is relatively unchanged. This action of angiotensin is dependent upon an intact sympathetic nervous system. The direct vasoconstrictor action of angiotensin is not an essential part of the enhanced response. The phenomenon was shown to have relevance to acute and chronic experimental renal hypertension in dogs by the fact that in both the pressor response to tyramine was enhanced. We believe that the ability of angiotensin to intensify the effect of normal neurogenic vasomotor activity, along with an upward reset of the carotid sinus buffer mechanism, might account importantly for the neurogenic component of renal hypertension.

Normotensive condition restored by reno-portal venous shunt in experimental renal hypertension in dogs

With the use of our dermo-carotid artery bridge method, it has been made possible to measure the systolic and diastolic blood pressure indirectly by auscultation with no anesthesia, continuously, in any body position, any time and with a very simple apparatus for a long period of time. Through a marked decrease in the blood pressure was noted in the renal hypertensive dog after completion of a reno-portal venous shunt, such mechanism is assumed to be caused by the detoxifying process of the liver and by improvement of the renal blood flow.

Treatment and prophylaxis of experimental renal hypertension with renin.

Abstract Chronic experimental renal hypertension in dogs has been successfully treated with crude and semipurified hog renins and chronic experimental renal hypertension in dogs has been prevented by prophylaxis with crude and semipurified hog renins. These therapeutic and prophylactic effects are well-correlated with the antirenin titer. This evidence for antirenin (or an antibody to a protein closely related to renin) as the mechanism of the antihypertensive effects of hog renins constitutes support for the affirmative of the long-standing controversy regarding the primary role of renin (or some closely related protein) in the pathogenesis of experimental renal hypertension. Hog renal medulla contains a factor which interferes with the antihypertensive effects of hog renin in experimental renal hypertension in the dog by a mechanism presently unknown. Renotoxic and renal protective factors have been found to occur in fractions of renal extracts. Toxicity consists in increased and protection in decreased incidence of uremia after constriction of the renal arteries. After further preliminary experiments in animals, the possible pathogenetic role of the kidney in essential hypertension will be studied by passive immunization of patients with purified antirenin to human renin.

Pantothenic acid deficiency in experimental renal hypertension in dogs.

Pantothenic acid deficiency in experimental renal hypertension in dogs.

Obstruction of the common bile duct in experimental renal hypertension in dogs.

The frequency of arterial hypertension in subchronic atrophy of the liver is very low in relation to what might be expected according to the age-distribution of the patients. The hypothesis was established that a severely damaged liver function may prevent the development of arterial hypertension, or may obviate an already existing hypertension, and that a normal or only slightly inhenced liver function is a necessary condition for the development of hypertension.Summarizing, it can be said about the results of our experiments that 6 hypertensive dogs (with experimental, rend hypertension according to Goldblatt's method!) -4 having had hypertension of short duration, 2 having had a more prolonged hypertension -displayed a gradual fall of the blood pressure towards or down to the normal, pre-operative values after obstruction of the common bile duct had been established. These blood pressure falls were observed in clogs in good health, which were sufficiently fed.In one dog biliary cirrhosis with ascites a...

The intrarenal pressure during experimental renal hypertension.

The intrarenal interstitial pressure was measured during the course of experimental renal hypertension in dogs. In perinephritic hypertension, produced by wrapping the kidney in a cellophane bag, the intrarenal pressure rose slowly from the normal value of 25 mm. Hg to a final level of about 60 mm. Hg. Strong pressure pulsations were observed in the renal parenchyma during this type of hypertension. In the hypertension following partial occlusion of the renal artery, the intrarenal pressure remained approximately normal, except in malignant hypertension when it tended to decline to about 9 mm. Hg. The hypertension of perinephritis is interpreted as a consequence of renal ischemia, the high intrarenal pressure, produced by the constricting fibrotic hull, acting to reduce the effective perfusion pressure of the kidney. The two experimental hypertensions herein examined are considered as examples of influent resistance hypertensions and effluent resistance hypertensions, the former being due to renal arterial or arteriolar resistance and the latter due to renal venous resistance, specifically at the arcuate-interlobar junction. The application of this concept to renal hypertensive disease in man is discussed.

A note on the effect of a vitamin K-like quinone upon experimental renal hypertension in dogs: Oppenheimer, B. S., and Zacharias, L.: J. Mt. Sinai Hosp. 14:542 (Sept.-Oct.), 1947

A note on the effect of a vitamin K-like quinone upon experimental renal hypertension in dogs: Oppenheimer, B. S., and Zacharias, L.: J. Mt. Sinai Hosp. 14:542 (Sept.-Oct.), 1947

Effect of Total Sympathectomy on Experimental Renal Hypertension in Dogs.

SummaryIn one dog with sustained hypertension established by application of Goldblatt clamps to both renal arteries, total sympathectomy produced a moderate drop in the blood pressure, which, however, has remained well above the control level. In another dog, previously sympathectomized, hypertension could be produced by bilateral application of Goldblatt clamps.