The Renin System for Understanding Human Hypertension: Evidence for Blood Pressure Control by A Bipolar Vasoconstriction-Volume Mechanism. Prorenin as a Determinant of Renin Secretion

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Abstract
A body of evidence indicates that all hypertensive phenomena ranging from mild disorders to fulminant malignant hypertension can be profitably analyzed by assessing the relative contribution of two final determinants of the arterial blood pressure – the degree of arteriolar vasoconstriction and size of the volume filling the arterial tree. The latter function is largely determined by the state of sodium balance. Renin-sodium profiling and separate testing with specific pharmacologic probes are the basic tools for quantifying these factors in individual patients. This bidimensional analysis of blood pressure phenomena has considerable practical value for identifying and treating curable renovascular and adrenocortical forms. Beyond this, the analysis provides pathophysiologic information of practical value for characterizing and treating individual patients in the whole spectrum of human hypertensive diseases including essential hypertension. This new analytical scaffold also identifies key physiologic questions for future research. About 90 percent of the circulating renin occurs in an inactive form as a possible prorenin, which could be an important regulatory point for renin release. in response to stimuli prorenin rises and falls with active renin. Beta blockade may lower active renin by blocking the conversion process. At the physiological level the activation and/or release of renin appears to be primarily determined by sodium-volume changes perceived by a distal tubular mechanism.