Genetic linkage of albuminuria and renal injury in Dahl salt-sensitive rats on a high-salt diet: comparison with spontaneously hypertensive rats

2004 ◽  
Vol 18 (2) ◽  
pp. 218-225 ◽  
Author(s):  
Anja-Kristin Siegel ◽  
Peter Kossmehl ◽  
Michael Planert ◽  
Angela Schulz ◽  
Markus Wehland ◽  
...  
Keyword(s):  
Renal Injury ◽  
Spontaneously Hypertensive Rats ◽  
High Salt ◽  
Hypertensive Rats ◽  
Tubulointerstitial Injury ◽  
High Salt Diet ◽  
Salt Diet ◽  
Spontaneously Hypertensive ◽  
Damage Indices ◽  
Salt Sensitive Hypertension

Our aim was to study the effects of high-salt diet on the genetics of albuminuria and renal injury in the Dahl salt-sensitive (SS) rat. We compared SS with salt-resistant spontaneously hypertensive rats (SHR) and with genetically related salt-sensitive stroke-prone SHR (SHRSP). Moreover, we performed genome-wide linkage analysis to identify quantitative trait loci (QTL) contributing to salt-induced renal injury in an F2 population derived from SS and SHR ( n = 230). In response to high-salt diet SS and SHRSP developed a striking increase in systolic blood pressure, urinary albumin excretion (UAE), and renal damage indices compared with SHR. Both SHRSP and SS developed severe glomerulosclerosis, whereas microangiopathy, tubulointerstitial fibrosis, and inflammation were more pronounced in SHRSP. We detected two QTL with significant linkage to UAE on rat chromosomes (RNO) 6 and 19. Comparison with the recently identified salt-independent UAE QTL in young animals revealed that the UAE QTL on RNO6 is unique to high-salt conditions, whereas RNO19 plays a significant role during both low- and high-salt conditions. Some F2 animals demonstrated severe microangiopathy and tubulointerstitial injury, which exceeded the degree observed in the parental SS strain. Three loci demonstrated suggestive linkage to these phenotypes on RNO3, RNO5, and RNO20, whereas no linkage to glomerular damage was found. Further analyses at these loci indicated that the severity of renal injury was attributable to the SHR allele. Our data suggest that the SHR genetic background confers greater susceptibility for the development of microangiopathy and tubulointerstitial injury in salt-sensitive hypertension than the SS background.

scholarly journals Effects of Valsartan on Mechanical Properties of the Carotid Artery in Spontaneously Hypertensive Rats Under High-Salt Diet

Hypertension ◽  
2001 ◽  
Vol 38 (3) ◽  
pp. 439-443 ◽  
Author(s):  
Carlos Labat ◽  
Patrick Lacolley ◽  
Malika Lajemi ◽  
Marc de Gasparo ◽  
Michel E. Safar ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Carotid Artery ◽  
Spontaneously Hypertensive Rats ◽  
High Salt ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
Spontaneously Hypertensive

The Hypertensive Role of the Kidney in Spontaneously Hypertensive Rats

1973 ◽  
Vol 45 (s1) ◽  
pp. 135s-139s ◽  
Author(s):  
G. Bianchi ◽  
U. Fox ◽  
G. F. Di Francesco ◽  
U. Bardi ◽  
Maria Radice
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
High Salt ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
Spontaneously Hypertensive ◽  
Wistar Strain

1. Spontaneously hypertensive and normotensive rats were selectively bred from a single Wistar strain. 2. Cross-transplantation of kidneys from hypertensive to normotensive rats and vice versa was performed, the sole remaining kidney of the recipient later being excised. Kidneys were also transplanted from normotensive donors into normotensive recipients and from hypertensive to hypertensive. 3. Normotensive rats receiving a kidney from either a hypertensive or normotensive donor showed unchanged blood pressure on normal salt diet. High-salt diet produced a greater rise in recipients of hypertensive than in recipients of normotensive kidneys. 4. Normotensive kidneys reduced the blood pressure of hypertensive recipients, but transplanted hypertensive kidneys had no such effect.

scholarly journals Posterior reversible encephalopathy syndrome in stroke-prone spontaneously hypertensive rats on high-salt diet

2018 ◽  
Vol 39 (7) ◽  
pp. 1232-1246 ◽  
Author(s):  
Fanny Herisson ◽  
Iris Zhou ◽  
Jerome Mawet ◽  
E Du ◽  
Arnavaz H Barfejani ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Small Vessel Disease ◽  
High Salt ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
Spontaneously Hypertensive ◽  
Posterior Reversible Encephalopathy ◽  
Vessel Disease ◽  
Reversible Encephalopathy

Stroke-prone spontaneously hypertensive rats (SHRSP) on high-salt diet are characterized by extremely high arterial pressures, and have been endorsed as a model for hypertensive small vessel disease and vascular cognitive impairment. However, rapidly developing malignant hypertension is a well-known cause of posterior reversible encephalopathy syndrome (PRES) in humans, associated with acute neurological deficits, seizures, vasogenic cerebral edema and microhemorrhages. In this study, we aimed to examine the overlap between human PRES and SHRSP on high-salt diet. In SHRSP, arterial blood pressure progressively increased after the onset of high-salt diet and seizure-like signs emerged within three to five weeks. MRI revealed progressive T2-hyperintense lesions suggestive of vasogenic edema predominantly in the cortical watershed and white matter regions. Histopathology confirmed severe blood–brain barrier disruption, white matter vacuolization and microbleeds that were more severe posteriorly. Hematological data suggested a thrombotic microangiopathy as a potential underlying mechanism. Unilateral common carotid artery occlusion protected the ipsilateral hemisphere from neuropathological abnormalities. Notably, all MRI and histopathological abnormalities were acutely reversible upon switching to regular diet and starting antihypertensive treatment. Altogether our data suggest that SHRSP on high-salt diet recapitulates the neurological, histopathological and imaging features of human PRES rather than chronic progressive small vessel disease.

Response of resistance arteries to reduced PO2 and vasodilators during hypertension and elevated salt intake

1997 ◽  
Vol 273 (2) ◽  
pp. H869-H877 ◽  
Author(s):  
Y. Liu ◽  
K. T. Fredricks ◽  
R. J. Roman ◽  
J. H. Lombard
Keyword(s):  
Skeletal Muscle ◽  
Salt Intake ◽  
High Salt ◽  
Nitric Oxide Donor ◽  
Resistance Arteries ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Membrane Function ◽  
Salt Diet ◽  
Spontaneously Hypertensive

This study assessed vasodilator responses in skeletal muscle resistance arteries (100-250 microns) from rats with chronic (4-8 wk) reduced renal mass (RRM) hypertension and normotensive sham-operated controls on a high (4% NaCl; HSSHAM)- or low (0.4% NaCl; LSSHAM)-salt diet. Arteries from RRM hypertensive rats [normal and high-salt diet (HSRRM)] and a separate group of spontaneously hypertensive rats exhibited an impaired dilation in response to reduced PO2 compared with those of their normotensive controls. Prostacyclin release, assessed by radio-immunoassay for 6-ketoprostaglandin F1 alpha, increased significantly in response to reduced PO2, but was unaffected by hypertension or salt intake. Dilator responses to acetylcholine and the prostacyclin analog iloprost were significantly reduced in both HSRRM and HSSHAM compared with LSSHAM rats. Dilation in response to direct activation of adenylate cyclase with forskolin or guanylate cyclase with the nitric oxide donor sodium nitroprusside was not significantly different in HSRRM, HSSHAM, and LSSHAM rats. These results indicate that hypoxic dilation is impaired in skeletal muscle resistance arteries of hypertensive rats and that chronic high-salt diet alone leads to impaired vasodilator responses in resistance arteries of normotensive animals, possibly via abnormalities in membrane function or G protein signaling rather than impaired second-messenger function.

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.

Post-cyclosporine-mediated hypertension and nephropathy: amelioration by vascular endothelial growth factor

2001 ◽  
Vol 280 (4) ◽  
pp. F727-F736 ◽  
Author(s):  
Duk-Hee Kang ◽  
Yoon-Goo Kim ◽  
Takeshi F. Andoh ◽  
Katherine L. Gordon ◽  
Shin-Ichi Suga ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
High Salt ◽  
Vascular Endothelial ◽  
Tubulointerstitial Injury ◽  
Angiogenic Growth Factors ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension ◽  
Endothelial Growth Factor

Recent studies have demonstrated a role for microvascular and tubulointerstitial injury in some models of salt-sensitive hypertension. We utilized a model of post-cyclosporin A (CsA) nephropathy and hypertension to test the hypothesis that treatment with an angiogenic factor aimed at ameliorating the microvascular and renal injury would prevent the development of hypertension. CsA was administered with a low-salt diet for 45 days, resulting in a renal lesion characterized by afferent arteriolopathy, focal peritubular capillary loss, and tubulointerstitial fibrosis. Rats were then placed on a high-salt diet and randomized to receive either vascular endothelial growth factor (VEGF121) or vehicle for 14 days. Placement of rats with established CsA nephropathy on a high-salt diet results in the rapid development of salt-sensitive hypertension. VEGF121 treatment resulted in lower blood pressure, and this persisted on discontinuing the VEGF. VEGF121 treatment was also associated with a decrease in osteopontin expression, macrophage infiltration, and collagen III deposition and markedly stimulated resolution of the arteriolopathy (20.9 ± 7.8 vs. 36.9 ± 6.1%, VEGF vs. vehicle, P < 0.05). In conclusion, CsA-associated renal microvascular and tubulointerstitial injury results in the development of salt-sensitive hypertension. Treatment of animals with established CsA nephropathy with VEGF reduces the hypertensive response and accelerates histological recovery. The vascular protective effect of VEGF may be due to the improvement of arteriolopathy. Angiogenic growth factors may represent a novel strategy for treating CsA-associated hypertension and renal disease.

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