Sex-dependent Effects of Nephron Ift88 Disruption on Blood Pressure, Renal Function and Cystogenesis

2021 ◽  
pp. ASN.2020111571
Author(s):  
Chunyan Hu ◽  
Jayalakshmi Lakshmipathi ◽  
Elizabeth Binning ◽  
Kelly Hyndman ◽  
Deborah Stuart ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Primary Cilia ◽  
Plasma Renin ◽  
Cyst Formation ◽  
Renal Physiology ◽  
No Production ◽  
Polycystic Kidneys ◽  
Nitrite Nitrate ◽  
And Control

Background: Primary cilia regulation of renal function and blood pressure (BP) in health and disease is incompletely understood. The current study investigated the effect of nephron ciliary loss on renal physiology, blood pressure and ensuing cystogenesis. Methods: Mice underwent doxycycline (DOX)-inducible nephron-specific knockout (KO) of the Ift88 gene at 2 months of age using a Cre-LoxP strategy. Blood pressure, kidney function, and renal pathology were studied 2 and 9 months after DOX (Ift88 KO) or vehicle (control). Results: At 2 months post DOX, male, but not female, Ift88 KO, compared to sex-matched control, mice had reduced BP, enhanced salt-induced natriuresis, increased urinary nitrite/nitrate (NOx) excretion, and increased kidney NOS3 levels which localized to the outer medulla; the reductions in BP in male mice were prevented by L-NAME. At 9 months post DOX, male, but not female, Ift88 KO mice had polycystic kidneys, elevated BP and reduced urinary NOx excretion. No differences were observed in plasma renin concentration, plasma aldosterone, urine vasopressin or urine PGE2 between Ift88 KO and control mice at 2 or 9 months post DOX. Conclusions: Nephron cilia disruption in male, but not female, mice: 1) reduces BP prior to cyst formation; 2) increases NOx production that may account for the lower BP prior to cyst formation; and 3) induces polycystic kidneys that are associated with hypertension and reduced renal NO production.

Cardiovascular and renal control in NOS-deficient mouse models

2003 ◽  
Vol 284 (3) ◽  
pp. R628-R638 ◽  
Author(s):  
Pablo A. Ortiz ◽  
Jeffrey L. Garvin
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Cardiac Function ◽  
Knockout Mice ◽  
Vascular Tone ◽  
Single Gene ◽  
No Production ◽  
Compensatory Mechanisms ◽  
Nos Isoforms ◽  
Regulation Of Vascular Tone

Nitric oxide (NO) plays an essential role in the maintenance of cardiovascular and renal homeostasis. Endogenous NO is produced by three different NO synthase (NOS) isoforms: endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS). To investigate which NOS is responsible for NO production in different tissues, NOS knockout (−/−) mice have been generated for the three isoforms. This review focuses on the regulation of cardiovascular and renal function in relation to blood pressure homeostasis in the different NOS−/− mice. Although regulation of vascular tone and cardiac function in eNOS−/− has been extensively studied, far less is known about renal function in these mice. eNOS−/− mice are hypertensive, but the mechanism responsible for their high blood pressure is still not clear. Less is known about cardiovascular and renal control in nNOS−/− mice, probably because their blood pressure is normal. Recent data suggest that nNOS plays important roles in cardiac function, renal homeostasis, and regulation of vascular tone under certain conditions, but these are only now beginning to be studied. Inasmuch as iNOS is absent from the cardiovascular system under physiological conditions, it may become important to blood pressure regulation only during pathological conditions related to inflammatory processes. However, iNOS is constitutively expressed in the kidney, where its function is largely unknown. Overall, the study of NOS knockout mice has been very useful and produced many answers, but it has also raised new questions. The appearance of compensatory mechanisms suggests the importance of the different isoforms to specific processes, but it also complicates interpretation of the data. In addition, deletion of a single gene may have physiologically significant effects in addition to those being studied. Thus the presence or absence of a specific phenotype may not reflect the most important physiological function of the absent gene.

P3568The relationship between plasma renin and aldosterone levels and the reduction of blood pressure with spironolactone in patients with resistant hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Obertynska
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Resistant Hypertension ◽  
Antihypertensive Effect ◽  
Plasma Renin ◽  
Excellent Correlation ◽  
Chemical Evaluation ◽  
Pressure Lowering ◽  
Aldosterone To Renin Ratio ◽  
Treat All

Abstract The group of patients with resistant hypertension (RH) is not homogeneous on concentration of renin and aldosterone (AS). A lot of studies have shown that spironolactone (SP) was by far the most effective blood pressure-lowering treatment for patients with RH. However, it has been unknown whether SP would be the most effective in patients with different plasma renin profile. The aim was to determine whether plasma renin and AS predict the most effective treatment of SP. Methods 79 patients with RH were included in the study (a mean of 3.4±1.4 drugs per patient including diuretic, ACE-I or an ARB). The plasma AS and active renin concentration (ARC), the plasma aldosterone-to-renin ratio (ARR) were estimated at baseline. After chemical evaluation patients started on SP treatment with a mid-dose 25 mg daily (range 12.5–50 mg). At baseline and after 12 weeks of therapy patients underwent clinic and 24-hour BP measurement, also hematocrit, potassium (K), serum creatinine (C), eGFR were checked. Results In patients with RH the ARC varied widely and they were divided into low 46%, normal 29% and high renin 25% subgroups. All groups of patients had similar AS levels. Patients with high renin hypertension (HRH) had significantly worse renal function than patients with low renin (LRH) or normal renin hypertension (NRH), also hematocrit were significantly higher in HRH patients than in patients with LRH and NRH. At baseline in patients with RH was an excellent correlation between ARC and eGFR (P<0.001). After SP in whole group, the change from baseline in the clinic BP was −13.4/−6.8 mm Hg (P<0.0001 for both) and in 24-hour BP was −10.6/−6.1 mm Hg (P<0.001 for both), but patients with HRH showed less efficacy than patients with LRH and NRH (−5.4/−3.1 mm Hg; P<0.05 for both) and in 24-hour BP was −4.8/−2.9 mm Hg (P<0.05 for both). Moreover, in HRH patients the hematocrit and C levels increased significantly after the start of SP (P<0.001; P<0.0001 respectively). By regression analysis in whole group patients RH ARC and AS levels were not associated with the changes in BP, only eGFR was significantly associated with BP change for DBP (0.391, P<0.05); in patients with LRH and NRH was a mild relation between the change for SBP and ARR (P<0.05 for both), but not for HRH patients. Conclusion SP showed additional antihypertensive effect in the whole group of patients with RH, but in patients with HRH was less effective than in patients with LRH and NRH and lead to the worsening of renal function. In the whole group of patients with RH plasma renin and aldosterone levels were not associated with BP response to SP, but the change in DBP was correlated with baseline eGFR. Only in patients with LRH and NRH was a mild association between BP response to SP and ARR. So, we can't treat all RH patients with the help of one universal algorytm and treatment should be tailored to each patient according to neurohumoral profile and renal function.

scholarly journals Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring

2010 ◽  
Vol 298 (5) ◽  
pp. R1421-R1427 ◽  
Author(s):  
Norma B. Ojeda ◽  
Thomas P. Royals ◽  
Joshua T. Black ◽  
John Henry Dasinger ◽  
Jeremy M. Johnson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Ang Ii ◽  
Enhanced Sensitivity ◽  
And Control

Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg·kg−1·day−1) for 1 wk. Baseline blood pressures were similar between growth-restricted (112 ± 3 mmHg) and control (110 ± 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng·kg−1·min−1 for 30 min) was observed in growth-restricted (160 ± 2 mmHg) vs. control (136 ± 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 ± 2 mmHg) rats with no significant effect on blood pressure in controls (130 ± 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 μg/min) in control (184 ± 5 mmHg) and growth-restricted (184 ± 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR.

The Use of Frusemide and Propranolol in the Treatment of the Hypertension of Chronic Renal Disease

1974 ◽  
Vol 19 (1_suppl) ◽  
pp. 25-32 ◽  
Author(s):  
R. Wilkinson ◽  
Mary Pickering ◽  
Valerie Robson ◽  
R. W. Elliott ◽  
D. N. S. Kerr
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Renal Disease ◽  
Serum Creatinine ◽  
Marked Reduction ◽  
Chronic Renal Disease ◽  
Plasma Renin ◽  
Sodium Retention ◽  
Exchangeable Sodium ◽  
Standing Blood Pressure

Nine patients with renal disease, hypertension and impairment of renal function of varying degree have been studied before and during treatment with frusemide. In three patients observations were repeated following the addition of propranolol. In most cases frusemide resulted in a reduction of both lying and standing blood pressure but for the group the fall was not significant (P>0.05). In all patients a reduction in exchangeable sodium was achieved and the fall was significant for the group (P<0.05); this was accompanied by a significant increase in serum creatinine (P < 0.05). Plasma renin activity was increased in all patients during treatment with frusemide and the change for the group was significant (P<0.05). The addition of propranolol resulted in a marked reduction in renin in the three patients treated but in two blood pressure actually rose; in these two sodium retention had occurred following the introduction of propranolol.

scholarly journals CEP55 promotes cilia disassembly through stabilizing Aurora A kinase

2021 ◽  
Vol 220 (2) ◽  
Author(s):  
Yu-Cheng Zhang ◽  
Yun-Feng Bai ◽  
Jin-Feng Yuan ◽  
Xiao-Lin Shen ◽  
Yu-Ling Xu ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilia ◽  
Perinatal Death ◽  
Clinical Manifestations ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Mammalian Development ◽  
Polycystic Kidneys ◽  
And Control

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55−/− mice display clinical manifestations of Meckel–Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55−/− mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel–Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.

Effect of Percutaneous Transluminal Renal Angioplasty on Absolute Split Renal Function in Patients with Renovascular Hypertension. Influence of Age and Other Parameters

1993 ◽  
Vol 60 (1) ◽  
pp. 27-33
Author(s):  
M. Takeda ◽  
Y. Katayama ◽  
K. Saito ◽  
T. Tsutsui ◽  
T. Komeyama ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Plasma Renin ◽  
Artery Stenosis ◽  
Renal Angioplasty ◽  
Split Renal Function ◽  
Percutaneous Transluminal Renal Angioplasty ◽  
Percutaneous Transluminal

Tc99m-dimercaptosuccinic acid renal uptake (DMSA uptake) was examined to assess the changes in split renal function following percutaneous transluminal renal angioplasty (PTRA) in 9 patients with a total of 12 renal artery stenoses and renovascular hypertension (RVH). The results were studied with respect to age, degree of renal artery stenosis, and renal vein renin ratio (RVRR) before PTRA. Although the degree of renal artery stenosis, systolic blood pressure, and peripheral blood plasma renin activity were improved 3 months after PTRA, neither the DMSA uptake of the affected kidneys nor that of the contralateral kidneys improved. Although restenosis occurred during the long follow-up period in one patient, DMSA uptake did not change in parallel with the degree of stenosis or RVRR. The degree of improvement in DMSA uptake, blood pressure, and plasma renin activity after PTRA in patients aged under 70 years was significantly higher than that in patients 70 years or older. Good improvement of renal function was attained in a 4-year-old boy, despite the fact that split renal function prior to PTRA was so poor that nephrectomy had been considered instead of PTRA. These results suggest that several factors before PTRA, such as DMSA uptake, degree of renal artery stenosis, and RVRR, are not absolutely predictive of results after PTRA, and that the effect of PTRA on blood pressure and renal function is greater in younger patients.

Abstract P166: Kidney Changes In Patients With Morbid Obesity After Bariatric Surgery: Looking For The Mechanisms

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Anna Oliveras ◽  
Susana Vazquez ◽  
Isabel Galceran ◽  
Alberto Goday ◽  
Maria Vera ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Bariatric Surgery ◽  
Morbid Obesity ◽  
Renal Function ◽  
Body Weight ◽  
Plasma Renin ◽  
Homa Index ◽  
Anthropometric Parameters ◽  
Increased Risk ◽  
Renal Changes

Morbid obesity (MO) carries an increased risk of kidney damage. Albuminuria and hyperfiltration decrease after bariatric surgery (BS). The relationships between kidney changes obesity-associated are not fully understood. Aim: to analyze renal changes (Δ) and their determinants at 3-mths after BS (3m-postBS) in patients with MO. Methods: In a cohort of patients with MO, we analyzed changes in renal function at 3m-postBS and possible associations with anthropometric parameters, ambulatory blood pressure, glucose metabolism, adipocytokine profile, and components of both renin-angiotensin-aldosterone and endocannabinoid systems. Results: 59 patients were included, 76% women; age (mean ± SD): 42.3 ± 9.5 years; body weight (mean ± SD): 117.8 ± 19.2 Kg. At 3m-postCxB, significant reductions in body weight and waist circumference were observed (p <0.001), but not in blood pressure. Biochemical changes (mean, 95% CI); eGFR-CKDEPI: -4.6 mL/min/1.73m 2 (-8.6; -0.6), p = 0.024; Na + : 2.5 mmol/L (1.9; 3.0), p <0.001; K + : -0.2 mmol/L (-0.3; -0.1), p = 0.006; HbA1c: -0.47% (-0.63; -0.31), p <0.001 and HOMA-IR-Index: -3.13 (-4.19; -2.06), p <0.001. Δ of Albuminuria: Z-1.8 (p = 0.069). The Δ of eGFR-CKDEPI indirectly correlated only with the Δ of plasma renin activity (PRA), p = 0.026. The Δ of albuminuria indirectly correlated with the Δ of leptin (p = 0.039) and directly with the Δ of HbA1c (0.019), HOMA-index (p = 0.013), ACE2 (p = 0.032) and resistin (p = 0.005), as well as with the Δ of the endocannabinoids N-palmitoyl ethanolamine (p = 0.028) and N-stearoyl ethanolamine (p = 0.022). None of the factors analyzed was associated with changes in sNa + . The reduction in sK + was significantly correlated with the Δ of leptin (p = 0.028) and with the Δ of aldosterone (p = 0.025). In multivariate analyzes, no factor was independently associated with the different markers of renal function. Conclusions: patients with MO experience a decrease in eGFR-CKDEPI associated with an increase in PRA 3m-postBS, indicating that the hyperfiltration present in MO has a hemodynamic origin. On the other hand, the variation in albuminuria is related to the improvement of the carbohydrate metabolism and probably certain cytokines and endocannabinoids have a role, although the latter needs to be confirmed.

Renal Effects of Angiotensin I-Receptor Blockade and Angiotensin Convertase Inhibition in Man

1996 ◽  
Vol 90 (3) ◽  
pp. 205-213 ◽  
Author(s):  
Francois Schmitt ◽  
Svetlozar Natov ◽  
Frank Martinez ◽  
Bernard Lacour ◽  
Thierry P. Hannedouche
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Plasma Renin Activity ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Renin Activity ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibition

1. The objective was to compare two means of inhibition of the renin—angiotensin system [angiotensin-converting enzyme inhibition and selective antagonism of angiotensin II subtype 1 (AT1) receptor] on renal function in 10 healthy normotensive volunteers on a normal sodium diet. Since mechanisms of action may differ between both drugs, a synergistic action was further studied by combining the two drugs. 2. The design was a double-blind randomized acute administration of either placebo or a single oral dose of enalapril, 20 mg, followed in each case by administration of the AT1 selective antagonist losartan potassium, 50 mg orally. 3. The methods included measurements of hormones (plasma renin activity, plasma aldosterone), blood pressure and renal function from 45 to 135 min after administration of placebo or enalapril, and from 45 to 135 min after losartan and placebo or losartan and enalapril. Renal function was studied using clearance of sodium, lithium, uric acid, inulin and para-aminohippuric acid. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was determined and sieving curves were applied on a hydrodynamic model of ultrafiltration. 4. Losartan did not change plasma renin activity, blood pressure or glomerular filtration rate, but increased significantly renal plasma flow and urinary excretion of sodium and uric acid. Enalapril increased plasma renin activity and renal plasma flow, and decreased blood pressure without natriuretic, lithiuretic or uricosuric effects. The renal vasodilatation was potentiated when losartan and enalapril were combined, despite a further rise in plasma renin. In contrast to enalapril, losartan either alone or in combination with enalapril significantly depressed fractional clearances of dextran of small radii (34–42 Å). These changes in fractional clearances of dextran were presumably related to the rise in glomerular plasma flow since the other major determinants of filtration, i.e. transcapillary glomerular pressure gradient, ultrafiltration coefficient and membrane property, were computed as unchanged by either losartan, enalapril or a combination of both. 5. In conclusion, these findings suggest that in normal sodium-repleted man the renal, hormonal and blood pressure effects of AT1 antagonism and angiotensin-converting enzyme inhibition are not strictly similar and could be synergistic.

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