Plasma Levels of Prorenin and Renin in Blacks and Whites: Their Relative Abundance and Associations With Plasma Aldosterone Concentration

Abstract

Renin occupies a pivotal position in the generation of angiotensin II and production of aldosterone. Although all renin is derived from prorenin, the prorenin-to-renin ratio tends to differ among individuals with various clinical conditions. 1,2 Elevated levels of prorenin relative to renin can be found, for example, in diabetics with microvascular disease. 3-5 A (pro)renin receptor allows prorenin to display full enzymatic activity. 6 Transgenic rats overexpressing the (pro)renin receptor have elevated aldosterone levels, 7,8 and (pro)renin receptor gene polymorphisms not only associate with blood pressure but also with serum aldosterone levels 9,10 consistent with intra-adrenal, angiotensin II-stimulated aldosterone production. Since blacks, in comparison to whites, are more likely to have an expanded extracellular volume, 11 they tend to have lower levels of plasma renin activity (PRA). 12 Despite the lower renin levels in blacks, Sealey and colleagues noted that blacks and whites had similar levels of prorenin and angiotensinogen. 13 It is unclear, however, whether the disproportionate plasma prorenin and renin levels have differential effects on aldosterone, the final product of the renin-angiotensin-aldosterone system (RAAS), in blacks and whites.We sought in this study to determine if there is a relationship of volume to the relative proportion of renin-to-total renin (total renin consisting of renin and prorenin with the preponderance being prorenin). In other words, does a higher volume accompany a lower level of prorenin? Blacks, serving as the volume expanded group, were compared to whites. All subjects were healthy and thus unaffected by antihypertensive treatment. We measured PRA and the plasma concentrations of renin (PRC), levels of prorenin, angiotensinogen, and plasma aldosterone concentration (PAC), thus allowing for a comparison of the plasma levels of prorenin and renin, the reninto-total renin ratios, and the effects of prorenin and renin on aldosterone production in subjects of the two race groups. MethodsStudy protocol. Subjects were participants of an ongoing observational study which started in 2009. Upon enrollment, 129 subjects came to Indiana University Medical Center for 1 Department of medicine, Indiana University school of medicine, Indianapolis, Indiana, UsA; 2 regenstrief Institute, Inc., Indianapolis, Indiana, UsA; 3 roudebush Veteran Administration medical Center, Indianapolis, Indiana, UsA Background All renin arises from prorenin. the proportion of renin relative to prorenin could influence overall renin-angiotensin-aldosterone activity. We sought to determine whether prorenin levels were related to extracellular volume, as reflected by the levels of plasma renin activity (prA), and to aldosterone.

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

“…Patients with high plasma renin activity (PRA) respond well to RAAS blockers, some of which suppress renin release 59– 62 . For example, patients with elevated renin had a greater BP-lowering response to atenolol, an agent that suppresses renin release, than a diuretic 60, 61 .…”

“…However, all of those factors are likely interrelated. For instance, AAs have lower renin activity than do whites and have been shown to respond better to atenolol 62, 86 . Patients on a low-salt diet have higher renin activity 57 .…”

Hypertension

“…Retrospective analyses of BP trials confirmed this concept. 61,62 In addition, Gupta et al observed that African Americans, who on average have lower renin levels compared with Caucasians, 63 responded less well to atenolol. 64 Yet, others observed either no role for baseline renin, 65 or at most a weak trend.…”

Dysregulated aldosterone secretion in persons of African descent with endothelin-1 gene variants

“…In our total HyperPATH cohort study, we confirmed that ALDO, PRA, and potassium levels on a LIB salt diet were lower in AD than ED, as has been shown by others (1)(2)(3)(4)(5)(6)24). Because of limited genotyping data, we also performed analyses in a 2:1 restricted subcohort.…”

“…Compared with persons of European descent (ED), individuals of African descent (AD) are known to: (i) be more susceptible to cardiovascular disease (CVD); (ii) have a greater frequency of hypertension (HTN) (particularly salt-sensitive HTN); (iii) have more cardiovascular (CV) damage with HTN; (iv) have lower plasma renin activity (PRA); and (v) more resistant HTN (1)(2)(3)(4)(5)(6). Of interest, these same characteristics also are associated with increased aldosterone (ALDO) production, e.g., primary aldosteronism.…”