Abstract 500: The Cardiorenal Effects Of An Angiotensin Receptor Blocker (Valsartan) And Neprilysin Inhibitor (AHU377) Co-administered Daily For 6 Weeks In The Dahl Salt-sensitive Rat Model Of Volume-dependent Hypertension

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Alexander J McNamara ◽  
Laxminarayan G Hegde ◽  
Uwe Klein ◽  
Craig Hill ◽  
Cecile Yu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Weight Gain ◽  
Rat Model ◽  
Renal Injury ◽  
Body Weight Gain ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Neprilysin Inhibitor

The endogenous natriuretic peptide system helps maintain cardiovascular homeostasis by counterbalancing the deleterious effects of renin angiotensin system activation. This study examined whether the co-administration of an ARB (valsartan: VAL) with a NEPi (AHU377: AHU) can reduce cardiorenal disease progression in the Dahl salt-sensitive (Dahl/SS) rat model of volume-dependent hypertension. Methods: Studies were conducted in conscious Dahl/SS hypertensive rats that were maintained on a high salt diet and surgically implanted with telemetry transmitters for monitoring blood pressure. Rats were treated for 6 weeks with either vehicle, VAL (30 mg/kg, PO) or VAL+AHU (30 + 30 mg/kg, PO). Changes in cardiac and renal functions were measured via Left Ventricle (LV) pressure-volume loops and biomarkers (KIM-1, NGAL and osteopontin). Results: Dahl/SS rats maintained on a high salt diet exhibited a progressive decrease in body weight gain, progressive increases in blood pressure and elevation of plasma and urinary biomarkers indicative of cardiac stress or renal injury. VAL and VAL+AHU both improved body weight gain and blunted the progressive hypertension. However, the magnitude of the antihypertensive effect was greater for VAL+AHU (peak change: - 33 ± 3 mmHg) than for VAL alone (peak change: -15 ± 5 mmHg). VAL+AHU treatment provided greater renal protective effects, based on renal biomarkers KIM-1 (286 ± 29 vs. 341 ± 59 ng), NGAL (58 ±9 vs. 108 ± 28 μg) and osteopontin (1637 ± 372 vs 2155 ± 748 ng), than VAL alone. The VAL+AHU treatment group demonstrated a greater normalization in LV function, with improved systolic contractility over VAL alone (preload-adjusted PWR max = 1 ± 0.1 vs. 2 ± 0.5 μWatt/uL). Most notably, the VAL+AHU group exhibited a greater survival rate (94%: 15 of 16) than either the VAL (75%: 12 of 16) or vehicle (70%: 14 of 20) groups. Conclusion: In summary, chronic co-administration of an ARB and NEPi to Dahl/SS rats significantly attenuated progression of hypertension, suppressed increases in biomarkers indicative of renal injury, improved cardiac function and increased overall survival. These results suggest that co-administration of an ARB and NEPi may confer a beneficial therapeutic strategy for the treatment of cardiorenal disease.

Abstract 16835: Targeted Disruption of Paraoxonase 3 in a Dahl Salt-Sensitive Rat Model of Chronic Kidney Disease Increases Renal Cortical Pro-Inflammatory Eicosanoids

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Chrysan J Mohammed ◽  
Fatimah K Khalaf ◽  
Prabhatchandra Dube ◽  
Tyler J Reid ◽  
Jacob A Connolly ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Injury ◽  
Renal Cortex ◽  
High Salt ◽  
High Density Lipoproteins ◽  
Wild Type ◽  
Targeted Disruption ◽  
High Salt Diet ◽  
Salt Diet ◽  
Mediators Of Inflammation

Background: Paraoxonase 3 (Pon3), is one of the three isoforms of the paraoxonase gene family. While Pon1 and Pon2 are widely studied, there is a paucity of knowledge regarding Pon3. Pon3 is synthesized in the liver and can circulate bound to high-density lipoproteins. There is significant expression in the kidney also. Pon3 has the ability to metabolize eicosanoids, which can act as signaling molecules and have known roles in the pathophysiology of some renal diseases. Decreased Pon activity is associated with elevated levels of eicosanoid metabolites and adverse clinical outcomes. We tested the hypothesis that targeted disruption of Pon3 results in elevated levels of pro-inflammatory eicosanoids and progression of renal injury. Methods/ Results: Ten week old male Dahl salt-sensitive (SS rats) and Pon3 mutant rats (SS Pon3 KO) were maintained on 8% high salt diet for eight weeks, to initiate salt-sensitive hypertensive renal disease. Previously we observed that SS Pon3 KO rats on eight weeks high salt diet demonstrated significantly increased phenotypic renal injury and mortality. In the current study, we noted that SS Pon3 KO had significantly decreased (p<0.05) glomerular filtration rate compared to SS wild type. Blood pressure (radiotelemetry) as well as plasma angiotensin and aldosterone (LC-MS/MS) were not different between the two groups after high salt diet. We used targeted lipidomic profiling to determine eicosanoid content in renal cortex from SS Pon3 KO and SS wild type rats at the end of eight weeks of high salt diet. We found that hydroxyl fatty acids 5-HEPE and 5-HETE (5-lipoxygenase dependent arachidonic acid metabolites) were significantly (p<0.05) elevated in the renal cortex of SS Pon3 KO compared to SS wild type rats. In addition to being mediators of inflammation, these metabolites are associated with renal cell injury and death. Furthermore, prostaglandin 6-keto-PGF 1α , which has known links to renal inflammation, was significantly (p<0.05) increased in renal cortex of SS- Pon3 KO compared to SS wild type rats. Conclusion: These findings suggest that targeted deletion of Pon3 increases pro-inflammatory eicosanoids (5-HETE and 5-HEPE) and prostaglandins (6-keto-PGF 1α ), as well as increases renal damage independent of blood pressure.

scholarly journals Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats

2020 ◽  
Vol 21 (6) ◽  
pp. 2248 ◽  
Author(s):  
Abu Sufiun ◽  
Asadur Rahman ◽  
Kazi Rafiq ◽  
Yoshihide Fujisawa ◽  
Daisuke Nakano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythm ◽  
Renal Injury ◽  
Tissue Injury ◽  
Renal Tissue ◽  
High Salt ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
The Difference

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet (HSD; 8% NaCl) for 10 weeks, followed by a transition to a normal salt diet (NSD; 0.3% NaCl) for 4 weeks. At baseline, NSD-fed DSS rats showed a dipper-type circadian rhythm of BP. By contrast, HSD for 5 days caused a significant increase in the difference between the active and inactive periods of BP with an extreme dipper type of BP, while proteinuria and renal tissue injury were not observed. Interestingly, HSD feeding for 10 weeks developed hypertension with a non-dipper pattern of BP, which was associated with obvious proteinuria and renal tissue injury. Four weeks after switching to an NSD, BP and proteinuria were significantly decreased, and the BP circadian rhythm returned to the normal dipper pattern. These data suggest that the non-dipper pattern of BP is associated with the progression of renal injury during the development of salt-dependent hypertension.

scholarly journals Fetal programming effects of pentaerythritol tetranitrate in a rat model of superimposed preeclampsia

2020 ◽  
Vol 98 (9) ◽  
pp. 1287-1299
Author(s):  
Andy W. C. Man ◽  
Min Chen ◽  
Yawen Zhou ◽  
Zhixiong Wu ◽  
Gisela Reifenberg ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucose Tolerance ◽  
Fetal Growth ◽  
Rat Model ◽  
High Salt ◽  
Pentaerythritol Tetranitrate ◽  
High Salt Diet ◽  
Blood Pressure Elevation ◽  
Salt Diet ◽  
Normal Chow

Abstract Preeclampsia is a common medical condition during pregnancy and a major cause of maternal and prenatal mortality. The present study was conducted to investigate the effects of maternal treatment with pentaerythritol tetranitrate (PETN) in Dahl salt-sensitive rats (DSSR), a model of superimposed preeclampsia. F0 parental DSSR were treated with PETN (50 mg/kg) from the time point of mating to the end of lactation. Maternal PETN treatment improved fetal growth and had no effect on blood pressure in DSSR offspring fed with normal chow or high-salt diet. Upon high-fat diet (HFD) feeding, offspring from PETN-treated mother showed improved glucose tolerance despite similar weight gain. Unexpectedly, maternal PETN treatment significantly potentiated the HFD-induced blood pressure elevation in male DSSR offspring. Endothelium-derived hyperpolarization factor (EDHF)-mediated vasodilation was similar between NCD-fed and HFD-fed control offspring but was markedly reduced in HFD-fed PETN offspring. EDHF genes were downregulated in the vasculature of HFD-fed PETN offspring, which was associated with epigenetic changes in histone modifications. In conclusion, maternal PETN treatment in DSSR shows both beneficial and unfavorable effects. It improves fetal growth and ameliorates glucose tolerance in the offspring. Although maternal PETN treatment has no effect on blood pressure in offspring fed with normal chow or high-salt diet, the offspring is at higher risk to develop HFD-induced hypertension. PETN may potentiate the blood pressure response to HFD by epigenetic modifications of EDHF genes. Key messages The core findings of this article suggest that maternal PETN treatment of DSSR, a rat model of a spontaneous superimposed preeclampsia, leads to • Improvement of fetal growth; • No changes of maternal blood pressure or markers of preeclampsia; • Amelioration of HFD-induced glucose intolerance in adult offspring; • No changes in blood pressure development of the offspring on normal chow or high salt-diet; • Potentiation of blood pressure elevation of the offspring on HFD.

scholarly journals Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats

2018 ◽  
Vol 132 (11) ◽  
pp. 1179-1197 ◽  
Author(s):  
Sarah C. Ray ◽  
Bansari Patel ◽  
Debra L. Irsik ◽  
Jingping Sun ◽  
Hiram Ocasio ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Bicarbonate ◽  
Renal Injury ◽  
High Salt ◽  
Proton Channel ◽  
Pathological Feature ◽  
Glomerular Injury ◽  
High Salt Diet ◽  
Salt Diet ◽  
Inflammatory Status

Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.

Mycophenolate mofetil prevents salt-sensitive hypertension resulting from nitric oxide synthesis inhibition

2001 ◽  
Vol 281 (1) ◽  
pp. F38-F47 ◽  
Author(s):  
Yasmir Quiroz ◽  
Héctor Pons ◽  
Katherine L. Gordon ◽  
Jaimar Rincón ◽  
Maribel Chávez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mycophenolate Mofetil ◽  
Washout Period ◽  
Renal Injury ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Histology ◽  
Salt Sensitive Hypertension

Recent studies have suggested that subtle microvascular and tubulointerstitial injury in the kidney can cause salt-sensitive hypertension. To test this hypothesis, we determined whether the mild renal disease induced by transient blockade of nitric oxide (NO) synthesis would result in salt-sensitive hypertension and whether prevention of the renal injury by coadministration of the immunosuppressive agent mycophenolate mofetil (MMF) would block the development of salt sensitivity. N ω-nitro-l-arginine-methyl ester (l-NAME; 70 mg/100 ml in the drinking water) was administered for 3 wk to rats with or without MMF (30 mg · kg−1 · day−1 by gastric gavage), followed by a 1-wk “washout” period in which the MMF was continued, which was followed in turn by placement on a high-salt (4% NaCl) diet for an additional 4 wk. Renal histology was examined at 3 and 8 wk, and blood pressure was measured serially.l-NAME treatment resulted in acute hypertension and the development of mild renal injury. During the washout period, blood pressure returned to normal, only to return to the hypertensive range on exposure of the animals to a high-salt diet. MMF treatment prevented the development of hypertension in response to a high-salt diet. This correlated with the ability of MMF to inhibit specific aspects of the renal injury, including the development of segmental glomerulosclerosis, the infiltration of T cells and ANG II-positive cells, and the thickening of afferent arterioles.

scholarly journals Antihypertensive and Antihyperlipidemic Activity of Aqueous Methanolic Extract of Rauwolfia Serpentina in Albino Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094207
Author(s):  
Syed Muhammad Ali Shah ◽  
Syed Ali Raza Naqvi ◽  
Naveed Munir ◽  
Sohaib Zafar ◽  
Muhammad Akram ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
High Salt ◽  
Herbal Extract ◽  
Albino Rats ◽  
Therapeutic Effects ◽  
High Salt Diet ◽  
Salt Diet ◽  
Rauwolfia Serpentina ◽  
Wide Range

Rauwolfia serpentina has a wide range of therapeutic effects so this study was planned to explore the antihypertensive and antihyperlipidemic therapeutic responses of R serpentina doses using albino rats by measuring the blood pressure, biochemical parameters, and histological architecture of liver and kidney tissues. Thirty albino rats were divided into 5 groups (n = 6) as G1 (normal Control) received normal diet, G2 (positive control) received only 8% NaCl added diet (high salt diet); G3 was given atenolol (standard drug control) 50 mg/kg body weight, G4 and G5 groups were given methanolic plant extract as low dose (100 mg/kg body weight) and high dose (200 mg/Kg body weight) daily along with high salt diet for 4 weeks, respectively. Rauwolfia serpentina significantly ( P < .05) decreased the blood pressure in G4 and G5 groups as compared to G2 and G3. Significant ( P < .05) impact was reported, on serum lipid profile and serum proteins as well as hepatoprotective and renoprotective potential on studying tissues sections under microscope, in animal groups given herbal extract as compared to control groups. It could be concluded that R serpentina has therapeutic effect to manage the hypertension and hypercholesterolemia most probably via protecting the liver and renal architectures.

Fenofibrate lowers blood pressure in two genetic models of hypertension

2000 ◽  
Vol 78 (5) ◽  
pp. 367-371 ◽  
Author(s):  
Raied Khaled Shatara ◽  
Dale W Quest ◽  
Thomas W Wilson
Keyword(s):  
Blood Pressure ◽  
Weight Gain ◽  
High Salt ◽  
Lipid Lowering ◽  
Urine Protein ◽  
High Salt Diet ◽  
Salt Diet ◽  
Urine Protein Excretion ◽  
Protein Excretion ◽  
Sd Rats

Fenofibrate, a commonly used lipid lowering drug, induces the expression of the gene coding for cytochrome P450-4A, whose major product is 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a potassium channel antagonist, could increase or decrease blood pressure (BP). We studied the effects of four weeks of oral fenofibrate on BP, urine output (UVol), plasma renin activity (PRA), and urine protein excretion in young (4-5 weeks) stroke prone spontaneously hypertensive rats (SHRSP), older (25 weeks) SHRSP, Dahl salt sensitive rats (Dahl S) on a high salt diet, Dahl S rats on a normal salt diet, and normotensive Sprague-Dawley (SD) rats. Fenofibrate prevented the increase in BP in 4-5 week old SHRSP, reduced BP in 25 week old SHRSP, but had no effect on BP in normotensive SD rats. Similarly, fenofibrate prevented the increase in BP in Dahl S rats on a high salt diet, but had no effect in Dahl S rats on a low salt diet. Fenofibrate increased UVol (and reduced weight gain) in young SHRSP and tended to increase it in other groups. It also increased PRA 2 to 5-fold in all groups except older SHRSP. Young SHRSP receiving fenofibrate excreted significantly less urine protein than control rats. The drug reduced proteinuria in Dahl S rats on high salt diet, but had no significant effect on proteinuria in other groups. In summary, fenofibrate reduced blood pressure and weight gain, increased UVol and PRA, and reduced urine protein excretion in young SHRSP. Other groups of animals showed these changes to a variable, but directionally similar extent. These findings are consistent with a natriuretic effect of fenofibrate. Key words: hypertension, animal models, natriuresis, fenfibrate, lipid lowering agents.

Abstract 4394: Chronic Administration of Urocortin 2 Prevents the Development of Heart Failure in an Animal Model of Hypertensive Heart Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Silvia Meili-Butz ◽  
Marco Studer ◽  
Dietlinde John ◽  
Christian Morandi ◽  
Matthias Pfisterer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Animal Model ◽  
Body Weight ◽  
Heart Disease ◽  
Hypertensive Heart Disease ◽  
Chronic Administration ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet

Background: Recently, novel corticotropin-releasing factor (CRF)-related peptides named Urocortin (Ucn) 1, 2, and 3 were described. Available data suggest that the Ucns are part of a peripheral CRF system modulating cardiovascular function and mediating cardiovascular responses to stress. Chronic Ucn2 administration induced sustained blood pressure lowering and prevented the development of left ventricular hypertrophy (LVH) in an animal model of hypertensive heart disease. However, no data are available whether chronic administration of Ucn2 may prevent the progression from LVH to heart failure. Methods: Experiments were performed in Dahl salt-sensitive rats. Animals were fed a high salt diet containing 4% NaCl to induce arterial hypertension, LVH, and heart failure. From the phase of LVH on (after 7 weeks of high salt diet), animals were injected with either Ucn2 at a dose of 2.5 μg/kg body weight or vehicle b.i.d. Animals underwent repetitive tail cuff blood pressure measurements and echocardiographic analysis of LV dimension and function at baseline (prior to first injection of Ucn2) and after 5 weeks of b.i.d. treatment with Ucn2. Results: Results are given in the following table as mean (± SD). No differences in heart weight/body weight ratios between Ucn2- and vehicle treated animals were found after 5 weeks of treatment. Conclusion: Chronic CRF receptor stimulation by Ucn2 in the severely hypertensive Dahl salt-sensitive rat, an animal model of hypertensive heart disease, prevents the progression from LVH to LV dilatation and the deterioration of LV function. Thus, chronic administration of Ucn2 might represent a novel approach to the prevention of heart failure.

scholarly journals Evaluation of metalloprotease inhibitors on hypertension and diabetic nephropathy

2011 ◽  
Vol 300 (4) ◽  
pp. F983-F998 ◽  
Author(s):  
Jan M. Williams ◽  
Jin Zhang ◽  
Paula North ◽  
Steven Lacy ◽  
Michael Yakes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Combined Therapy ◽  
High Salt ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet ◽  
Albumin Excretion ◽  
Mmp Inhibitor

This study examined the effects of two new selective metalloprotease (MMP) inhibitors, XL081 and XL784, on the development of renal injury in rat models of hypertension, Dahl salt-sensitive (Dahl S) and type 2 diabetic nephropathy (T2DN). Protein excretion rose from 20 to 120 mg/day in Dahl S rats fed a high-salt diet (8.0% NaCl) for 4 wk to induce hypertension. Chronic treatment with XL081 markedly reduced proteinuria and glomerulosclerosis, but it also attenuated the development of hypertension. To determine whether an MMP inhibitor could oppose the progression of renal damage in the absence of changes in blood pressure, Dahl S rats were fed a high-salt diet (4.0% NaCl) for 5 wks to induce renal injury and then were treated with the more potent and bioavailable MMP inhibitor XL784 either given alone or in combination with lisinopril and losartan. Treatment with XL784 or the ANG II blockers reduced proteinuria and glomerulosclerosis by ∼30% and had no effect on blood pressure. Proteinuria fell from 150 to 30 mg/day in the rats receiving both XL784 and the ANG II blockers, and the degree of renal injury fell to levels seen in normotensive Dahl S rats maintained from birth on a low-salt diet. In other studies, albumin excretion rose from 125 to >200 mg/day over a 4-mo period in 12-mo-old uninephrectomized T2DN rats. In contrast, albumin excretion fell by >50% in T2DN rats treated with XL784, lisinopril, or combined therapy. XL784 reduced the degree of glomerulosclerosis in the T2DN rats to a greater extent than lisinopril, and combined therapy was more effective than either drug alone. These results indicate that chronic administration of a selective MMP inhibitor delays the progression, and may even reverse hypertension and diabetic nephropathy.

Abstract P267: Sex Differences in Cyp450 Activity and the Development of Hypertension and Renal Injury in the Dahl S Rat

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Wenjie Wu ◽  
Sydney Murphy
Keyword(s):  
Blood Pressure ◽  
Renal Injury ◽  
High Salt ◽  
Female Rats ◽  
Male Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Vessels ◽  
Female Relative ◽  
Renal Vascular

It is well documented that a sexual dimorphism exists in the regulation of blood pressure in both the human population as well as experimental animal models, however evidence of a sex difference is lacking in the Dahl S rat. Thus, we hypothesize that alterations in CYP450 expression and 20-HETE production contribute to the progression of renal injury in Dahl S rats. Consistent with what we have previously reported, no difference was noted in the blood pressure of male or female Dahl SSJr rat (213.8±12 vs 196.8±13 mmHg, ns) following 4 weeks of a high salt diet (8%NaCl). However, proteinuria (148±25 vs 355±22 mg/day, p<0.05) and renal injury (1.9±0.01 vs 2.5±0.2) were lower in female relative to male rats. In addition, GFR was significantly reduced in male vs female rats (392.4±89 vs 829.5±98 μl/min/g, p<0.05) following at high salt challenge. Renal cortical (11.3.8±16 vs 20.99±2.8 pmol/min/mg, p<0.05) and outer medullary (19.4±3 vs 6.9±1.8 pmol/min/mg, p<0.05) 20-HETE production was elevated in female versus male rats. Furthermore, renal vascular 20-HETE production was elevated in the renal vessels compared to males (0.53±0.23 vs 3.2±1.2 pmol/min/mg, p<0.05). Thus, alterations in the production of renal eicosanoids may contribute to the delay in renal injury in females relative to male Dahl SSJr rats. AHA 14SDG20160020

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