(pro)Renin Processing and Secretion in Black Essential Hypertension and Other Low-Renin Syndromes

Renin, it is now certain, plays an important role in a significant number of disorders, such as essential hypertension and diabetic hypertension in blacks. These disorders have been categorized along sharp renin lines: high, normal, and low renin subgroups (11,54). Renin initiates the cleavage of angiotensin I, which is subsequently converted to angiotensin II, a potent vasoconstrictor molecule that stimulates aldosterone and vasopressin secretion and salt and water retention. By initiating the cascade, renin is therefore a significant factor in the physiological manifestation of the renin—angiotensin—aldosterone system (RAAS). RAAS plays an important role in cardiovascular homeostasis and chemiosmotic (salt and water coupled to proton movement) balance, but renin secretion from the kidney is a key step in the system. There is general agreement that renin physiological inhibition (or its equivalent) provides rational therapeutic efficacy for high-renin essential hypertension (106). Calcium channel blockade has also been shown to provide satisfactory results, even in the low-renin subgroup where earlier therapeutic strategies have proven largely ineffective. In low-renin hypertension (LRH) and diabetic lowrenin hypertension (dLRH), characteristic of an increasing number of blacks, only recently has sufficient evidence been accumulated to target specific molecules controlling renin secretion at the cellular level, thereby opening the way for novel approaches to drug development. It is clear that calcium and chemiosmotic forces are central to the control of renin secretion and that the renin profiles observed in some renin disorders may reflect abnormal control at specific sites along the secretory cascade (33). This chapter surveys briefly the current state of knowledge in the low-renin subgroup, as it relates to renin and prorenin [(pro)Renin] processing, storage, and secretion. We also focus on theories of (pro)Renin secretion in an attempt to describe the sites of control (and thereby prime targets of abnormal function as evidenced by examples of lowrenin syndromes [LRS]) (27), and consider briefly the prospects and sites of action of the most successful therapeutic agents used to address LRH and dLRH.