Renin and aldosterone and the pathogenesis of hypertensive vascular damage

Arterial hypertension often leads to vascular injury that clinically may be expressed as malignant hypertension, heart attack, stroke, or nephrosclerosis. Many different mechanisms have been suggested to operate in the various types of hypertensive disease that cause vascular lesions. Most of these incriminate either blood pressure elevations per se as a mechanical stress upon the arterial wall or the direct vasculotoxic action of an overactive renin-angiotensin system affecting the structure and the permeability of the small vessels, or a combination of these two factors. These theories are supported by the finding of more frequent cardiovascular complications in the high-renin hypertensive patients, while low-renin patients appear relatively protected. However, both experimentally and clinically similar types of vascular lesions may be encountered in conditions characterized by the absence of abnormally increased renin-angiotensin or even in the absence of blood pressure elevation. For the most part, however, vascular damage that is produced without the participation of the renin-angiotensin component can be directly related to salt excess induced by mineralocorticoid excess and amplified by attendant renal damage.This review analyzes the evidence accumulated from studying the sequence of events leading to vascular damage in experimental models that express pathogenetically different types of hypertension, i.e., vasoconstrictor hypertension due mainly to arteriolar constriction induced by clamping of a renal artery with angiotensinemia (renindependent) and volume hypertension due mainly to arterial overfilling, induced by administration of salt with a mineralocorticoid (salt-dependent). It is noteworthy that in both models, the onset of malignant vascular changes is marked by the sudden occurrence of profuse diuresis accompanied by loss of sodium, decrease in body weight, and evidence of hemoconcentration.On the basis of these observations, a unifying theory is presented to explain the occurrence of similar lesions as they develop in these two different types of hypertension. Both forms induce arteriolar narrowing, impaired arteriolar wall and tissue perfusion, transudation, plasmatic vasculosis, pressure natriuresis, hemoconcentration, fibrin deposition, and, finally, fibrinoid necrosis. In the case of salt hypertension, vasoconstriction may not be present, but it is replaced by edema of the arteriolar wall. With this hypothesis, all vascular changes in chronic hypertension can be explained in terms of an inappropriate interaction between a vasoconstrictor component (largely angiotensin) and a volume factor (determined by renal excretory capacity modulated by aldosterone).