Pathogenesis of Malignant Hypertension

IN THE usual definition, the benign phase of essential hypertension is characterized by elevated diastolic pressure associated with diffuse vascular disease (arterial and arteriolar sclerosis) of unknown origin but without significant impairment of renal excretory function. Malignant hypertension has been defined in a variety of ways and there is no complete agreement about its pathognomonic features. The most common definition is that it usually represents an accelerated phase of benign essential hypertension, which was previously existent for a variable period, and that it is characterized by cerebral and ocular signs and symptoms as constant diagnostic features, with death occurring in a short time, usually from termiiial renal failure. The recent definition of malignant hypertension, proposed by the Medical Advisory Board of the Council for High Blood Pressure of the American Heart Association, is perhaps a happy compromise, for it reads: "A clinical phase, rarely occurring de novo, more often appearing after a primary or secondary hypertension, characterized by diastolic hypertension and by accelerated and progressive renal damage, usually (but not necessarily) accompanied by papilledema, often by retinal hemorrhages and 'exudate,' and giving rise to early death from uremia unless the course is terminated along the way by complicating brain or heart damage." There can be no great quarrel with this definition, even by those who stress the primary pathogenetic importance of the kidney, because there is no reference to the origin of the hypertension. There is even greater diversity of opinion about the pathogenesis of malignant hypertensioln than there is about the definition. Some consider it to be a form of essential hypertension, not of renal origin, but marked by renal excretory impairment occurring as a late or terminal manifestation; others (including the writer) believe that the malignant phase, like the benign, is primarily, and even more obviously, of renal origin. There are reasons, clinical, pathologic, and experimental, for this wide difference of view. One source of confusion has been the failure of many investigators to recognize that the pathologic changes of the kidneys in the malignant phase are neither uniform nor unique. Another source of difficulty has been lack of agreement about the nature and pathogenesis of the necrotizing arteriolar lesion that is found in the kidneys and other organs, and that is regarded by most investigators as a pathognomonic feature of malignant hypertension. Experimental investigations carried out on the rat have contributed to this confusion. In this animal, so-called "necrotizing arteriolitis" has been produced by a variety of means from injections of desoxycorticosterone acetate and methyl-androstenediol to repeated elevation of the blood pressure produced by intravenous injections of pitressin or by sudden injections of Ringer's solution directly into the systemic arterial stream. The fact is, however, that the rat is unusually susceptible to periarteritis nodosa, which usually involves arterial branches larger than the arterioles, and most investigators, unfortunately, have misinterpreted periarteritis nodosa as equivalent to, or identical with, arteriolar necrosis. To what extent the incidence and severity of spoIntaneous lesions may have been increased by these experimental procedures is not germane