Contribution of Circulating Angiotensinogen Concentrations to Variations in Aldosterone and Blood Pressure in a Group of African Ancestry Depends on Salt Intake

Michel, Fabrice; Norton, Gavin R.; Majane, Olebogeng H.I.; Badenhorst, M; Vengethasamy, Leanda; Paiker, Janice; Maseko, Muzi J.; Sareli, Pinhas; Woodiwiss, Angela J.

doi:10.1161/hypertensionaha.111.181230

Cited by 33 publications

(37 citation statements)

References 45 publications

(63 reference statements)

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“…Such patients have a greater propensity to target organ damage and demonstrate a better response to antihypertensive agents such as calcium channel blockers and diuretics than those targeting the RAAS 33, 34. However, the role of activation of the RAAS in salt‐sensitive hypertension in black human patients is currently debated 35. Similar to hypertensive black patients, cats demonstrate a limited antihypertensive response to ACEi therapy, but respond well to calcium channel blockade 7, 12.…”

Section: Discussionmentioning

confidence: 99%

Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate

Jepson

Syme

Elliott

2013

Veterinary Internal Medicne

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BackgroundRole of renin‐angiotensin aldosterone system (RAAS) in feline systemic hypertension is poorly understood.ObjectivesExamine plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) in normotensive and hypertensive cats with variable renal function and in response to antihypertensive therapy.AnimalsOne hundred and ninety‐six cats >9 years from first opinion practice.Methods PRA, PAC, and aldosterone‐to‐renin ratio (ARR) were evaluated in cats recruited prospectively and grouped according to systolic blood pressure (SBP) and renal function (nonazotemic normotensive [Non‐Azo‐NT], nonazotemic hypertensive [Non‐Azo‐HT], azotemic normotensive [Azo‐NT], azotemic hypertensive [Azo‐HT]). Changes in PRA and PAC were evaluated with antihypertensive therapy (amlodipine besylate).ResultsPlasma renin activity (ng/mL/h; P = .0013), PAC (pg/mL; P < .001), and ARR (P = 0.0062) differed significantly among groups. PRA (ng/mL/h) was significantly lower in hypertensive (Non‐Azo‐HT; n = 25, median 0.22 [25th percentile 0.09, 75th percentile 0.39], Azo‐HT; n = 44, 0.33 [0.15, 0.48]) compared with Non‐Azo‐NT cats (n = 57, 0.52 [0.28, 1.02]). Azo‐HT cats had significantly higher PAC (n = 22, 149.8 [103.1, 228.7]) than normotensive cats (Non‐Azo‐NT; n = 26, 45.4 [19.6, 65.0], Azo‐NT; n = 18, 84.1 [38.6, 137.8]). ARR was significantly higher in Azo‐HT (n = 20, 503.8 [298.8, 1511]) than Azo‐NT cats (n = 16, 97.8 [77.0, 496.4]). Significant increase in PRA was documented with antihypertensive therapy (pretreatment [n = 20] 0.32 [0.15–0.46], posttreatment 0.54 [0.28, 1.51]), but PAC did not change.Conclusions and Clinical ImportanceHypertensive cats demonstrate significantly increased PAC with decreased PRA. PRA significantly increases with antihypertensive therapy. Additional work is required to determine the role of plasma aldosterone concentration in the pathogenesis of hypertension and whether this relates to autonomous production or activation of RAAS without demonstrable increase in PRA.

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Section: Discussionmentioning

confidence: 99%

Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate

Jepson

Syme

Elliott

2013

Veterinary Internal Medicne

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“…First, whereas previous studies have alluded to the association of the AGT gene and BP regulation in populations of African ancestry, 10,11 Michel et al,5 in an attempt to study determinants of AGT, were not able to demonstrate the role of the AGT genotype in explaining the relationship among AGT, aldosterone, and BP. This is not entirely surprising given the limitation of the cross-sectional design of this study.…”

Section: See Related Article Pp 62-69mentioning

confidence: 96%

“…8 Dietary sodium intake and aldosterone may act in concert to accelerate TOD. 9 The findings of Michel et al 5 demonstrate that, in the particular situation of high dietary salt intake, despite the tendency to have a low-renin state, AGT participates in BP regulation in hypertensive black patients. This finding argues strongly for the need to control for dietary sodium intake in future studies evaluating the effects of RAAS on BP regulation in hypertensive blacks.…”

mentioning

confidence: 98%

“…The article by Michel et al, 5 in this issue of Hypertension, addresses the mechanism by which RAAS activation affects blood pressure (BP) regulation in a population of African ancestry. Specifically, the authors evaluated plasma renin, plasma angiotensinogen (AGT), and serum aldosterone concentrations in 579 South African blacks.…”

mentioning

confidence: 99%

“…Evaluation of a purely hypertensive cohort with a similar study design may mitigate this issue. Third, there is also the possibility of dysregulation in the production of AGT that was not addressed by Michel et al 5 It is important to consider the possibility of independent adipocyte secretion of aldosterone, 12 an especially important consideration in blacks in whom obesity is prevalent. Fourth, and perhaps most importantly, the study by Michel et al 5 fails to address the impact of the tissue-specific renin-angiotensin system and its contribution to circulating AGT.…”

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confidence: 99%

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Unraveling the Mechanism of Renin-Angiotensin- Aldosterone System Activation and Target Organ Damage in Hypertensive Blacks

Williams

Ogedegbe²

2012

Hypertension

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See related article, pp 62-69T he International Society on Hypertension in Blacks consensus statement in 2010 noted that, in the setting of high dietary sodium intake, hypertensive blacks have particularly impressive responses to renin-angiotensin-aldosterone system (RAAS) blockade. 1 The statement went on to point out that the excessive target-organ damage (TOD) in hypertensive blacks can be attributed to RAAS activation. Although a normal-to-"high-renin" hypertensive state is most prevalent, the classic hypertension literature has categorized blacks as typically having a "low-renin" state. 2 There is somewhat of a paradox in the observation that blacks, despite having a low-renin state, have high serum aldosterone concentrations. 3 Blacks experience disproportionately higher rates of hypertension-related TOD compared with whites. 4 The mediators of the higher rates of TOD noted in blacks are most likely directly attributed to high levels of downstream mediators of the RAAS, such as aldosterone and angiotensin II. The mechanism by which a low-renin state can be associated with such an apparently active RAAS is not clearly defined.The article by Michel et al, 5 in this issue of Hypertension, addresses the mechanism by which RAAS activation affects blood pressure (BP) regulation in a population of African ancestry. Specifically, the authors evaluated plasma renin, plasma angiotensinogen (AGT), and serum aldosterone concentrations in 579 South African blacks. They demonstrated an inverse relationship between plasma renin concentrations and BP (PϽ0.001) on one hand, as well as plasma renin concentrations and dietary sodium intake (24-hour urinary Na ϩ /K ϩ , PϽ0.0001) on the other hand. Despite this inverse relationship, there was a direct and independent association between AGT concentrations and systolic BP (PϽ0.005) in a subset of participants with urinary Na ϩ /K ϩ at or more than the sample median (proxy for high sodium intake). Furthermore, in this same subset, there was an independent and direct relationship between AGT and serum aldosterone concentrations (PϽ0.0001). This observation was strengthened by the incremental increase in the multivariate-adjusted relationship between AGT and both serum aldosterone concentrations and systolic BP across tertiles of urinary Na ϩ /K ϩ . These impressive relationships were not observed in the subset of participants with urinary Na ϩ /K ϩ less than the sample median.The primary function of circulating AGT is to act as a substrate for renin, resulting in the biologically active peptides angiotensin I and angiotensin II. It is important to appreciate that the Michaelis-Menten constant for the renin-AGT reaction approximates the concentration of circulating AGT. 6 Therefore, AGT concentrations, as opposed to renin concentrations, may be the rate-limiting factor in the generation of angiotensin I. Angiotensin II subsequently stimulates aldosterone secretion downstream in the RAAS cascade. Although the relationship between AGT and BP has been established for several decades,...

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A Consideration of Genetic Mechanisms Behind the Development of Hypertension in Blacks

Pratt

2013

Curr Hypertens Rep

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Hypertension is a more serious disease in blacks. The determinants of the blood pressure (BP) may be uniquely different from those in whites. The characteristic low-renin, salt-sensitive hypertension of blacks is consistent with the kidney reabsorbing additional sodium (Na), which leads to an expanded plasma volume that drives the BP. Mechanisms considered are genetically based. These include: (1) the intra-renal renin-angiotensin system (RAS), one based on molecular variations in angiotensinogen; (2) the Na, K, 2Cl cotransporter (NKCC2) and its regulators in the thick ascending limb, which are associated with a variety of phenotypes consistent with a more active cotransporter in blacks; and (3) the genes for MYH9 and APOL 1, which have been associated with kidney disease in blacks. To achieve a state of hypertension, an increase in Na uptake in proximal nephron regions may require a distal nephron that does not fully adjust due to less than adequate suppression of aldosterone production.

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Contribution of Circulating Angiotensinogen Concentrations to Variations in Aldosterone and Blood Pressure in a Group of African Ancestry Depends on Salt Intake

Cited by 33 publications

References 45 publications

Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate

Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate

Unraveling the Mechanism of Renin-Angiotensin- Aldosterone System Activation and Target Organ Damage in Hypertensive Blacks

A Consideration of Genetic Mechanisms Behind the Development of Hypertension in Blacks

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