Studies on Experimental Hypertension

Abstract

The production of the acute malignant phase of experimental hypertension has been accomplished in seventeen dogs. The method used to produce this type of hypertension was the same as for the benign type (4), namely, constriction of the main renal arteries, or the equivalent, constriction of the aorta above the origin of both main renal arteries, but the constriction was especially severe. The malignant phase in the animals was characterized by hypertension, terminal renal insufficiency and the development of petechiae and larger hemorrhages in many internal organs, especially the alimentary tract. These were due to dissecting hemorrhage through, or rupture of, the wall of severely hyalinized or necrotic arterioles, or rupture of capillaries. Hyalinization and necrosis of arterioles were more severe and more widespread in animals that had a period of benign hypertension before the onset of renal insufficiency. In animals with a previous long period of benign hypertension, thickening of the media also occurred in arterioles, with or without hyalinized intima. Elevation of blood pressure (mechanical factor) and renal insufficiency (humoral factor) are at least two of the necessary conditions for the development of the necrotic arterioles and hemorrhages. Necrotic arterioles and hemorrhages have not yet been observed in animals that have had very high blood pressure for years without renal insufficiency, nor in animals with azotemia, due to removal of both kidneys, but without hypertension. Hyalinized retinal arterioles have been observed in dogs with persistent hypertension and with moderate or no disturbance of renal function. That ischemia is not the cause of the necrosis of the arterioles is shown by their absence from the ischemic kidneys of the dogs and their widespread presence in other organs that were not ischemic. These experiments show that the necrotic arterioles and hemorrhages are secondary to and not the primary cause of the malignant phase of hypertension.

Lacunes.

“…The thickened arterial walls are thought to lose their ability to constrict, resulting in a resetting of cerebrovascular autoregulation at higher blood pressure levels. 3134 Continued high pressure produces increased capillary hydrostatic pressure with capillary damage, 36 an effect that does not occur in renal arteries protected from hypertension distal to an experimental arterial clamp 36 or to renal arterial stenosis. 30 The overdistension 3738 of these small arteries occurs in segmental fashion with vascular necrosis, [38][39][40] which allow red blood cells, plasma, and protein ultrafiltrates into the stretched segments of the wall.…”

“…41 That other vessels are spared such injury is not easily explained. However, some findings 36,42 suggest that larger vessels are able to absorb enough in the subintima and in their thicker muscularis to resist such change, while the tiny cerebral cortical arteries of a size similar to the penetrators are protected by their more distal location. 37 Lipohyalinosis*"-" shares with fibrinoid necrosis some of the same histochemical, 43 electron-microscopic, 36, ** and immunofiuorescent 46 characteristics.…”

Studies on renin: The duration of the pressor effect of large doses in conscious normal and renally abnormal dogs. Observations on anesthetized and uremic dogs, and the anaphylactic and pathological effects of pig renin

“…Similar reactions have been described in rabbits (19 (20). The necessary combination of severe renal insufficiency and hypertension in the etiology of the malignant syndrome of renally ischemic animals (21,22), has been questioned as the result of experiments on rats, in which only one renal artery was constricted (23,24).. In the present study, there are definite indications that heterologous renin can precipitate cardiac and gastro-intestinal hemorrhages and necroses, in some dogs without severe hypertension or renal insufficiency.…”

The Effect of Diet on the Pathological Changes in Rats With Nephrotoxic Nephritis

“…13) and probably were responsible for the intestinal lesion. Goldblatt 9 has recently reported that intestinal bleeding is one 2 I12 EFFECT OF DIET ON RATS WITH NEPHITMS of the cardinal signs of the malignant phase of hypertension in dogs. While blood pressure readings were not made in the present experiment, hypertension was previously demonstrated in rats with chronic progressive nephritis of nephrotoxic origin.3…”