8 Renin in essential hypertension

Abstract

The enzyme renin is responsible for initiating a sequence of reactions that leads to the formation of the peptide hormone angiotensin II, whose major properties include the ability to induce arteriolar vasoconstriction and to stimulate biosynthesis of aldosterone, the dominant mineralocorticoid hormone of the adrenal cortex. The discussion that follows will focus on the renin found in and secreted by the kidney and its relevance to the understanding of essential hypertension. While renin or renin-like enzymes have been identified in several other tissues, it is the enzyme of renal origin that is thought to be the principal source of the well-characterized circulating renin--angiotensin system. Based on several lines of evidence, some investigators have reasoned that the principal function of the renin--angiotensin system is the maintenance of fluid and electrolyte balance. Paramount among these is the profound influence of extracellular fluid volume on the secretion of renin, and the role of the system in regulating aldosterone secretion. In addition, the renin-angiotensin system appears quite early in phylogeny, since renin-like enzymes are found in association with the glomerulus of teleosts and even more primitive fish (Nishimura, 1980). It is thus conceivable that angiotensinlike peptides may have played some role in adaptation from marine to fresh water or terrestrial existence. However, as Nishimura (1980) points out, the phylogenetic appearance of a renin-secreting apparatus that is responsive to changes in renal perfusion pressure antedates the appearance of sodiumretaining steroids and of sodium-sensitive mechanisms governing renin secretion. Moreover, the fact that angiotensin exerts a vasopressor action throughout the vertebrate kingdom has led her to speculate that the renin system evolved in close relation to blood pressure homeostasis. In recent years, evidence has accumulated that confirms the role of the renin--angiotensin system in the physiological regulation of arterial pressure. Since renin secretion increases in the standing position, it is likely that this function may be of even greater importance in mammals that assume the erect posture. As a result, there has developed considerable interest in determining whether renin and angiotensin may play some role in the genesis of primary or essential hypertension.