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  • 1
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    Higher Maternal Cortisol Associated With Lower Blood Pressure in Offspring From 3 Months to 5 Years of Age in the Odense Child Cohort
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Hypertension Vol. 80, No. 4 ( 2023-04), p. 828-836
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 80, No. 4 ( 2023-04), p. 828-836
    Abstract: Synthetic glucocorticoid exposure in late pregnancy may be associated with higher blood pressure in offspring. We hypothesized that endogenous cortisol in pregnancy relates to offspring blood pressure (OBP). Objective: To investigate associations between maternal cortisol status in third trimester pregnancy and OBP. Methods: We included 1317 mother-child pairs from Odense Child Cohort, an observational prospective cohort. Serum (s-) cortisol and 24-hour urine (u-) cortisol and cortisone were assessed in gestational week 28. Offspring systolic blood pressure and diastolic blood pressure were measured at age 3, 18 months, and 3 and 5 years. Associations between maternal cortisol and OBP were examined by mixed effects linear models. Results: All significant associations between maternal cortisol and OBP were negative. In boys in pooled analyses, 1 nmol/L increase in maternal s-cortisol was associated with average decrease in systolic blood pressure (β=−0.003 mmHg [95% CI, −0.005 to −0.0003]) and diastolic blood pressure (β=−0.002 mmHg [95% CI, −0.004 to −0.0004] ) after adjusting for confounders. At 3 months of age, higher maternal s-cortisol was significantly associated with lower systolic blood pressure (β=−0.01 mmHg [95% CI, −0.01 to −0.004]) and diastolic blood pressure (β=−0.010 mmHg [95% CI, −0.012 to −0.011] ) in boys after adjusting for confounders, which remained significant after adjusting for potential intermediate factors. Conclusions: We found temporal sex dimorphic negative associations between maternal s-cortisol levels and OBP, with significant findings in boys. We conclude that physiological maternal cortisol is not a risk factor for higher blood pressure in offspring up to 5 years of age.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.122.20265
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2094210-2
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  • 2
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    Aldosterone, Salt, and Potassium Intakes as Predictors of Pregnancy Outcome, Including Preeclampsia
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Hypertension Vol. 74, No. 2 ( 2019-08), p. 391-398
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 74, No. 2 ( 2019-08), p. 391-398
    Abstract: The mineralocorticoid aldosterone increases in plasma in healthy pregnancy along with renin and angiotensin II and plays a key role in the physiological plasma volume expansion. In mice, aldosterone contributes to an optimal fetal development by enhancing PlGF (placental growth factor) expression and trophoblast cell proliferation. In preeclampsia, there is coincident suppression of aldosterone and impaired placental development. We hypothesized that aldosterone independently contributes to placental and birth weight in humans, and high dietary sodium and low potassium intakes affect this relationship adversely. We analyzed 24-hour urine collections and plasma samples from gestational week 29 in a subsample of 569 pregnant women from the Odense Child Cohort—a Danish population-based longitudinal cohort study. Plasma and urinary aldosterone were measured by ELISA, sodium and potassium excretions by flame photometer. Predictive values of aldosterone levels and sodium and potassium intakes were assessed by multiple and Cox regression analyses. Primary outcomes were placental weight and birth weight. Secondary outcome was preeclampsia. Urinary aldosterone excretion at gestational week 29 independently contributed to placental and birth weights (adjusted β-coefficients [95% CI], 24.50 [9.66–39.35] and 9.59 [4.57–14.61], respectively). Aldosterone levels were not associated to preeclampsia incidence. Salt intake 〉 6 g/d was associated with development of preeclampsia (hazard ratio [95% CI], 5.68 [1.51–21.36] ). At gestational week 29, urinary aldosterone excretion is an independent predictor of placental and birth weights. High salt intake is a risk factor for preeclampsia. In perspective, suppression of aldosterone in pregnancy has adverse trophic effects.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.119.12924
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2094210-2
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  • 3
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    Urine excretion of C3dg and sC5b-9 coincide with proteinuria and development of preeclampsia in pregnant women with type-1 diabetes
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of Hypertension Vol. 41, No. 2 ( 2023-02), p. 223-232
    Details
    In: Journal of Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 2 ( 2023-02), p. 223-232
    Abstract: Pregnant women with type-1 diabetes have an increased risk of preeclampsia with kidney injury and cardiovascular complications. Urine excretion of plasmin and soluble membrane attack complex (sC5b-9) is elevated in severe preeclampsia. We hypothesized a coupling between these events and that active plasmin promotes intratubular complement activation and membrane deposition. Methods: Stored urine and plasma samples from pregnant women with type-1 diabetes ( n  = 88) collected at gestational weeks 12, 20, 28, 32, 36 and 38 were used. In the cohort, 14 women developed preeclampsia and were compared with 16 nonpreeclampsia controls. Results: Urine C3dg and sC5b-9-associated C9 neoantigen/creatinine ratios increased and were significantly higher in women who developed preeclampsia. Plasma concentrations did not change with gestation. Urine plasmin(ogen) correlated to urine C3dg ( r  = 0.51, P   〈  0.001) and C9 neoantigen ( r  = 0.68, P   〈  0.001); urine albumin correlated to C3dg ( r  = 0.44, P   〈  0.001) and C9 ( r  = 0.59, P   〈  0.001). Membrane-associated C3dg and C9 neoantigen was detected in urinary extracellular vesicles from patients but not controls at 36 weeks. Receiver operating characteristic curves showed that C3dg and C9 neoantigen were inferior to albumin as predictive biomarkers for preeclampsia. Conclusion: In preeclampsia, urinary excretion of activated complement relates significantly to albuminuria and to plasmin(ogen) but not to activation in plasma. Intratubular complement activation in preeclampsia is a postfiltration event tightly related to proteinuria/plasminogenuria and a possible mechanistic link to cellular damage and kidney injury.
    Type of Medium: Online Resource
    ISSN: 0263-6352 , 1473-5598
    URL: Article
    DOI: 10.1097/HJH.0000000000003288
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2017684-3
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  • 4
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    Periarterial fat from two human vascular beds is not a source of aldosterone to promote vasoconstriction
    American Physiological Society ; 2018
    In:  American Journal of Physiology-Renal Physiology Vol. 315, No. 6 ( 2018-12-01), p. F1670-F1682
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 315, No. 6 ( 2018-12-01), p. F1670-F1682
    Abstract: Mouse adipocytes have been reported to release aldosterone and reduce endothelium-dependent relaxation. It is unknown whether perivascular adipose tissue (PVAT) releases aldosterone in humans. The present experiments were designed to test the hypothesis that human PVAT releases aldosterone and induces endothelial dysfunction. Vascular reactivity was assessed in human internal mammary and renal segmental arteries obtained at surgery. The arteries were prepared with/without PVAT, and changes in isometric tension were measured in response to the vasoconstrictor thromboxane prostanoid receptor agonist U46619 and the endothelium-dependent vasodilator acetylcholine. The effects of exogenous aldosterone and of mineralocorticoid receptor (MR) antagonist eplerenone were determined. Aldosterone concentrations were measured by ELISA in conditioned media incubated with human adipose tissue with/without angiotensin II stimulation. Presence of aldosterone synthase and MR mRNA was examined in perirenal, abdominal, and mammary PVAT by PCR. U46619 -induced tension and acetylcholine-induced relaxation were unaffected by exogenous and endogenous aldosterone (addition of aldosterone and MR blocker) in mammary and renal segmental arteries, both in the presence and absence of PVAT. Aldosterone release from incubated perivascular fat was not detectable. Aldosterone synthase expression was not consistently observed in human adipose tissues in contrast to that of MR. Thus, exogenous aldosterone does not affect vascular reactivity and endothelial function in ex vivo human arterial segments, and the tested human adipose tissues have no capacity to synthesize/release aldosterone. In perspective, physiologically relevant effects of aldosterone on vascular function in humans are caused by systemic aldosterone originating from the adrenal gland.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00391.2018
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2018
    detail.hit.zdb_id: 1477287-5
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  • 5
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    Blood Pressure and Angiogenic Markers in Pregnancy : Contributors to Pregnancy-Induced Hypertension and Offspring Cardiovascular Risk
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Hypertension Vol. 76, No. 3 ( 2020-09), p. 901-909
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 76, No. 3 ( 2020-09), p. 901-909
    Abstract: Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF [placental growth factor] and sFlt-1 [soluble fms-like tyrosine kinase-1] ) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associations: Girls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM: 1.81±0.59 and 2.11±0.59 mm Hg, respectively, all P 〈 0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM: 1.11±0.45 and 1.03±0.45, respectively, all P 〈 0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted β coefficients (95% CI) for predicting systolic blood pressure (SBP): −3.18 (−4.66 to −1.70) mm Hg, for predicting diastolic blood pressure (DBP): −2.48 (−3.57 to −1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.119.13966
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2094210-2
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  • 6
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    Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Journal of the American Society of Nephrology Vol. 20, No. 2 ( 2009-02), p. 299-310
    Details
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 20, No. 2 ( 2009-02), p. 299-310
    Type of Medium: Online Resource
    ISSN: 1046-6673
    URL: Article
    DOI: 10.1681/ASN.2008040364
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 2029124-3
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  • 7
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    Urine albumin is a superior predictor of preeclampsia compared to urine plasminogen in type I diabetes patients
    Elsevier BV ; 2018
    In:  Journal of the American Society of Hypertension Vol. 12, No. 2 ( 2018-02), p. 97-107
    Details
    In: Journal of the American Society of Hypertension, Elsevier BV, Vol. 12, No. 2 ( 2018-02), p. 97-107
    Type of Medium: Online Resource
    ISSN: 1933-1711
    URL: Article
    DOI: 10.1016/j.jash.2017.12.003
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 8
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    Natriuretic peptides relax human intrarenal arteries through natriuretic peptide receptor type‐A recapitulated by soluble guanylyl cyclase agonists
    Wiley ; 2021
    In:  Acta Physiologica Vol. 231, No. 3 ( 2021-03)
    Details
    In: Acta Physiologica, Wiley, Vol. 231, No. 3 ( 2021-03)
    Abstract: Natriuretic peptides, BNP and ANP increase renal blood flow in experimental animals. The signalling pathway in human kidney vasculature is unknown. It was hypothesized that BNP and ANP cause endothelium‐independent relaxation of human intrarenal arteries by vascular natriuretic peptide receptor‐A, but not ‐B and ‐C, which is mimicked by agonists of soluble guanylyl cyclase sGC. Methods Human (n = 54, diameter: 665 ± 29 µm 95% CI) and control murine intrarenal arteries (n = 83, diameter 300 ± 6 µm 95% CI) were dissected and used for force recording by four‐channel wire myography. Arterial segments were pre‐contracted, then subjected to increasing concentrations of BNP, ANP, phosphodiesterase 5‐inhibitor sildenafil, sGC‐activator BAY 60‐2770 and ‐stimulator BAY 41‐2272. Endothelial nitric oxide synthase (eNOS) dependence was examined by use of L‐NAME and eNOS knockout respectively. Molecular targets (NPR A‐C, sGC, phosphodiesterase‐5 and neprilysin) were mapped by PCR, immunohistochemistry and RNAscope. Results BNP, ANP, sildenafil, sGC‐activation and ‐stimulation caused concentration‐dependent relaxation of human and murine intrarenal arteries. BNP responses were independent of eNOS and were not potentiated by low concentration of phosphodiesterase‐5‐inhibitor, sGC‐stimulator or NPR‐C blocker. PCR showed NPR‐A and C, phosphodiesterase‐5, neprilysin and sGC mRNA in renal arteries. NPR‐A mRNA and protein was observed in vascular smooth muscle and endothelial cells in arteries, podocytes, Bowmans capsule and vasa recta. NPR‐C was observed in tubules, glomeruli and vasculature. Conclusion Activation of transmembrane NPR‐A and soluble guanylyl cyclase relax human preglomerular arteries similarly to phosphodiestase‐5 inhibition. The human renal arterial bed relaxes in response to cGMP pathway.
    Type of Medium: Online Resource
    ISSN: 1748-1708 , 1748-1716
    URL: Issue
    URL: Article
    DOI: 10.1111/apha.2021.231.issue-3
    DOI: 10.1111/apha.13565
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2617148-X
    detail.hit.zdb_id: 2219379-0
    SSG: 12
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  • 9
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    Protective effect of sacubitril/valsartan (Entresto) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy
    Oxford University Press (OUP) ; 2023
    In:  Nephrology Dialysis Transplantation Vol. 38, No. 1 ( 2023-01-23), p. 80-92
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. 1 ( 2023-01-23), p. 80-92
    Abstract: Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II–angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n = 6). Next, four groups of pigs were followed for 15 days (n = 24) after PN (one-third right kidney, 60 min ischaemia) + Entresto (49/51 mg/day; n = 8), PN + vehicle (n = 8), sham + Entresto (49/51 mg/day; n = 4) and sham + vehicle (n = 4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25 ± 6 mL/min, left 31 ± 7 mL/min) accounted for the total GFR (56 ± 14 mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23 ± 6 mL/min, P  & lt; .05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfac200
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 10
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    Functional adaptation after kidney tissue removal in patients is associated with increased plasma atrial natriuretic peptide concentration
    Oxford University Press (OUP) ; 2022
    In:  Nephrology Dialysis Transplantation Vol. 37, No. 11 ( 2022-10-19), p. 2138-2149
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 37, No. 11 ( 2022-10-19), p. 2138-2149
    Abstract: Following nephrectomy, the remaining kidney tissue adapts by an increase in glomerular filtration rate (GFR). In rats, hyperfiltration can be transferred by plasma. We examined whether natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) increase in plasma proportionally with kidney mass reduction and, if so, whether the increase relates to an increase in GFR. Methods Patients (n = 54) undergoing partial or total unilateral nephrectomy at two Danish centres were followed for 1 year in an observational study. Glomerular filtration rate was measured before, and 3 and 12 months after surgery. Natriuretic propeptides (proANP and proBNP) and aldosterone were measured in plasma before and at 24 h, 5 days, 21 days, 3 months and 12 months. Cyclic guanosine monophosphate (cGMP) was determined in urine. Results There was no baseline difference in GFR between total and partial nephrectomy (90.1 mL/min/1.73 m2 ± 14.6 versus 82.9 ± 18; P = 0.16). Single-kidney GFR increased after 3 and 12 months (12.0 and 11.9 mL/min/1.73 m2, +23.3%). There was no change in measured GFR 3 and 12 months after partial nephrectomy. ProANP and proBNP increased 3-fold 24 h after surgery and returned to baseline after 5 days. The magnitude of acute proANP and proBNP increases did not relate to kidney mass removed. ProANP, not proBNP, increased 12 months after nephrectomy. Plasma aldosterone and urine cGMP did not change. Urine albumin/creatinine ratio increased transiently after partial nephrectomy. Blood pressure was similar between the groups. Conclusion ANP and BNP increase acutely in plasma with no relation to degree of kidney tissue ablation. After 1 year, only unilateral nephrectomy patients displayed increased plasma ANP, which could support adaptation.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfab327
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1465709-0
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