Role of angiotensin II in potassium-mediated stimulation of aldosterone secretion in the dog.

Pratt, J. Howard

doi:10.1172/jci110661

Cited by 77 publications

(29 citation statements)

References 41 publications

(45 reference statements)

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“…Several explanations for the lower aldosterone secretion in blacks can be proposed: (a) AII may be lower in blacks than in whites but at the same time higher than physiologically appropriate for the level of accumulated sodium; (b) the expression of AGT may be greater in kidney than in liver where most circulating angiotensinogen originates; or (c) there may be different types and degrees of responsiveness to All in the kidney and the adrenal. In regard to the latter, the aldosterone secretory response to All is related to the prevailing potassium concentration (35,36), and blacks, in comparison with whites, may consume a diet lower in potassium, thereby reducing the effect of All on aldosterone secretion (37,38). Altematively, a higher angiotensinogen level in blacks may not contribute to sodium retention as much as result from it.…”

Section: Discussionmentioning

confidence: 99%

The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children.

Bloem¹,

Manatunga²,

Tewksbury³

et al. 1995

J. Clin. Invest.

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225

127

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The T235 allele of the angiotensinogen gene (AGT) has been associated with hypertension. Blood pressure increases faster over time in black children than in white children, and in adults hypertension is more prevalent in blacks. We sought evidence for a role for angiotensinogen to contribute to racial differences in blood pressure in a study of 148 white and 62 black normotensive children (mean age, 14.8 yr). The frequency of the T235 allele was 0.81 in blacks and 0.42 in whites (X2 = 77.3, P = 0.0001). The mean angiotensinogen level was 19% higher in blacks than in whites (P = 0.0001 for males, P = 0.004 for females). Genotype was positively related to serum angiotensinogen in white children (P = 0.0001 for males, P = 0.004 for females), but a similar relationship was absent in blacks where the frequency of M235 may have been too low to discern an association. Longitudinal blood pressure (measured twice yearly) adjusted for body mass index showed a marginally significant relationship to the angiotensinogen level (P = 0.07). An independent relationship of serum angiotensinogen with body mass index (P = 0.0001) and race (P = 0.0003) was also observed. In summary, T235 was more frequent, and the level of angiotensinogen was higher in blacks than in whites. Such a racial difference in the renin-angiotensin system may contribute to the disparity in blood pressure levels of white and black young people. (J. Clin. Invest. 1995. 95:948-953.)

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Section: Discussionmentioning

confidence: 99%

The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children.

Bloem¹,

Manatunga²,

Tewksbury³

et al. 1995

J. Clin. Invest.

Self Cite

225

127

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“…Increases in levels of plasma aldosterone were greater than those of PRA, possibly because of stimulation of aldosterone secretion by both angiotensin II and potassium. 17 Amiloride had a marginally significant main effect on systolic BP (Pϭ0.09) but not on diastolic BP (Pϭ0.14). Spironolactone had no main effect on either systolic (Pϭ0.69) or diastolic BP (Pϭ0.89).…”

Section: Responses To Treatmentmentioning

confidence: 95%

Blood Pressure Responses to Small Doses of Amiloride and Spironolactone in Normotensive Subjects

et al. 2001

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Abstract-The epithelial sodium channel (ENaC) is a principal site for sodium reabsorption and as such may participate importantly in blood pressure (BP) regulation. Amiloride, a direct inhibitor of ENaC, characteristically has mild antihypertensive properties, consistent with ENaC having more minor influences on BP regulation. Counter-regulatory influences may, however, prevent amiloride from effectively lowering BP. Aldosterone secretion is known to increase in response to the reduced sodium reabsorption that follows amiloride inhibition of ENaC, and because aldosterone upregulates ENaC function, we considered the possibility that secondary hyperaldosteronism mitigates the ability of amiloride to reduce BP. In the present study, the BP responses to amiloride (5 mg per day), spironolactone (25 mg per day), the combination of the 2 drugs, and placebo were studied in healthy normotensive subjects. Over 4 weeks of treatment, the combination of amiloride and spironolactone lowered systolic BP by 4.6Ϯ1.6 (meanϮSEM) mm Hg (Pϭ0.022) and diastolic BP by 2.2Ϯ1.2 mm Hg (Pϭ0.30), whereas either drug alone had no significant effect on BP.The findings suggest that the 2 drugs with different modes of action-amiloride, a direct inhibitor of ENaC, and spironolactone, a mineralocorticoid receptor antagonist-may compliment each other's ability to inhibit ENaC and thereby reduce sodium reabsorption to a point at which BP decreases. On the other hand, we cannot rule out that the BP response resulted from the greater dose of total drug. 4 -6 or the life-threatening decrease in blood pressure (BP) that occurs in the neonatal period known as pseudohypoaldosteronism type 1. 7 More minor but common molecular variations in ENaC may also affect risk for hypertension. 8,9 If, indeed, ENaC is important for maintaining BP or contributing to the high BP of some individuals, then giving amiloride, a direct inhibitor of ENaC, should effectively lower BP, but in general, it is weakly antihypertensive 10 -13 and used primarily in combination with a thiazide diuretic for its potassium-sparing actions. 11In the patients described by Liddle et al, 4 triamterene, also an inhibitor of ENaC, lowered BP but only after sodium intake was severely restricted. Sodium has been shown to interfere with the ability of amiloride to inhibit sodium conductance in vitro, 14 and thus amiloride may not lower BP because modern diets are high in sodium. An alternative theory is that the secondary increase in aldosterone secretion that occurs in response to amiloride abrogates the ability of amiloride to prevent sodium reabsorption. In the present study, we examined the effect on BP of combining amiloride and spironolactone, a mineralocorticoid antagonist. Using a 2ϫ2 factorial study design, the BP responses to amiloride alone, spironolactone alone, the combination of amiloride and spironolactone, and placebo were compared in normotensive subjects. Methods SubjectsThe study used 20 whites and 20 blacks, age 18 to 30, from a cohort followed as part of a study of BP reg...

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“…The plasma aldosterone increased more than PRA (level of aldosterone increased 3-fold after amiloride), most likely because of stimulation of aldosterone secretion by the increase in potassium and angiotensin II. 20 Systolic and diastolic BP decreased in the whites but not in the blacks after treatment for 1 week with amiloride ( Table 2). The racial differences in the BP responses were significant for both systolic (Pϭ0.034) and diastolic BP (Pϭ0.010).…”

Section: Responses To Amiloridementioning

confidence: 97%

Racial Difference in the Activity of the Amiloride-Sensitive Epithelial Sodium Channel

et al. 2002

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Abstract-Compared with whites, blacks appear to retain additional sodium that suppresses secretion of renin and aldosterone. The epithelial sodium channel (ENaC) is an aldosterone-regulated site for sodium reabsorption. ENaC activity could be higher in blacks, contributing to sodium retention or, alternatively, lower because of reduced stimulation by aldosterone. To examine the level of ENaC activity in blacks relative to whites, blood pressure (BP) responses to amiloride (5 mg/d), an inhibitor of ENaC, were measured in 20 black and 25 white normotensive young people. After 1 week, systolic BP decreased by 3.0Ϯ9.2 (SD) and diastolic by 2.8Ϯ8.3 mm Hg in the whites, whereas systolic BP increased by 2.5Ϯ7.1 and diastolic by 3.8Ϯ8.0 mm Hg in the blacks; the racial difference in the BP response was significant for both systolic (Pϭ0.034) and diastolic BP (Pϭ0.010). As ENaC activity increases, renal secretion of potassium increases proportionately, and in a larger sample of subjects, the urinary potassium excretion rate was lower in the blacks (nϭ301) than in the whites (nϭ461): 3.2Ϯ0.1 versus 3.8Ϯ0.1 mmol/mmol creatinine (Pϭ0.0001). The concentration of serum potassium was higher in the blacks (nϭ81) than in the whites (nϭ167)

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Role of angiotensin II in potassium-mediated stimulation of aldosterone secretion in the dog.

Cited by 77 publications

References 41 publications

The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children.

The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children.

Blood Pressure Responses to Small Doses of Amiloride and Spironolactone in Normotensive Subjects

Racial Difference in the Activity of the Amiloride-Sensitive Epithelial Sodium Channel

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