Impact of gender on the renal response to angiotensin II
Open accessAbstract
Background It is clear that women with renal disease progress to end stage at a slower rate than do men. We hypothesized that this protection may result from gender-mediated differences in responses to angiotensin II (Ang II), which has known hemodynamic effects that are thought to promote renal disease progression. We examined sex differences in renin-angiotensin system (RAS) function by measuring renal hemodynamic function and circulating plasma components of the RAS at baseline and in response to graded infusions of Ang II.Methods We studied two groups of normal healthy subjects, 24 men and 24 women, mean age 28 +/- 1 years, ingesting a controlled sodium and protein diet. We examined baseline concentrations of angiotensin converting enzyme, plasma renin activity, Ang II, and aldosterone. Inulin and paraaminohippurate clearance techniques were used to estimate effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) at baseline and in response to graded Ang II infusion (0.5, 1.5, and 2.5 ng/kg/min).Results Mean baseline values for mean arterial pressure and aldosterone were lower in women, whereas values for plasma Ang II, GFR, ERPF, and filtration fraction (FF) did not differ. In response to Ang II, both groups exhibited a similar increase in mean arterial pressure and a decline in ERPF. GFR was maintained during Ang II infusion only in men, resulting in an augmentation of FF. In women, GFR declined in parallel with ERPF, and the FF response was significantly blunted. 17beta-Estradiol plasma concentrations influenced the ERPF response to Ang II infusion, with higher levels predicting a blunting of the decrease. The GFR response was not affected.Conclusions The renal microcirculation in sodium-replete women may respond differently to Ang II than that of men, with the female sex predicting a lesser augmentation of FF and possibly a blunted increase in intraglomerular pressure. The mechanism remains obscure, but these contrasting responses may help to explain gender-mediated differences in renal disease progression.
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There are known sex differences in renal K+ handling, aldosterone concentration, and plasma K+ concentration.
“We refer to this as a model of a man, instead of more generally as a human model, due to the known sex differences in renal K+ handling [24–26], ALD concentration [27], and plasma K+ concentration [28], all of which affect K+ homeostasis.”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [27]
Premenopausal women exhibit 15-20% lower circulatory aldosterone than age-matched men.
“Premenopausal women exhibit 15–20% lower circulatory aldosterone than age-matched men.”
From Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications (2026) · cites this paper as [18]
In healthy individuals (n = 48, mean age 28 years, 50% women), plasma aldosterone levels were significantly lower in women.
“in healthy individuals (n = 48, mean age 28 years, 50% women), plasma aldosterone levels were significantly lower in women [ 18 ].”
From Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications (2026) · cites this paper as [18]
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“628 Sex differences have been reported in renal K handling [43–45], ALD 629 concentration [46], and plasma K concentration [29], all of which affect K 630 homeostasis.”
BackgroundKim, K. M., Hwang, E. J., Lee, S., & Yoon, J.-H. (2024) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-023-07102-5 · Cited by 9 · see citing works
Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications
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- Authors
- Miller, J. A., Anacta, L. A., & Cattran, D. C.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Miller, Judith A.
- ORCID
- Miller, Judith A.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 55
- Issue
- 1
- Pages
- 278-285
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W1999111122
- Cited by
- 255
- References
- 41
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 10 · 2023: 10 · 2022: 7 · 2021: 16 · 2020: 6 · 2019: 11 · 2018: 11 · 2017: 9 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 9 · 2012: 15
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Toronto
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal and Vascular Pathologies
- Keywords
- sex differences, angiotensin II, renin-angiotensin system, renal hemodynamics, glomerular filtration rate, effective renal plasma flow, filtration fraction, estradiol, aldosterone, plasma renin activity, angiotensin-converting enzyme, kidney disease progression, intraglomerular pressure
- MeSH terms
- Adult, Aldosterone, Angiotensin II, Blood Pressure, Estradiol, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Failure, Chronic, Peptidyl-Dipeptidase A, Male, Renal Circulation, Renin, Renin-Angiotensin System, Sex Characteristics, Renal Plasma Flow, Effective
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