Endothelin receptor A blockade reduces proteinuria and vascular hypertrophy in spontaneously hypertensive rats on high-salt diet in a blood-pressure-independent manner

2002 ◽  
Vol 103 (s2002) ◽  
pp. 385S-388S ◽  
Author(s):  
Jörg TRENKNER ◽  
Friedrich PRIEM ◽  
Christian BAUER ◽  
Hans-Hellmut NEUMAYER ◽  
Manfred RASCHAK ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Hypertensive Rats ◽  
Independent Manner ◽  
High Salt Diet ◽  
Salt Diet ◽  
Spontaneously Hypertensive ◽  
Protein Excretion ◽  
Pressure Independent

The renal endothelin (ET) system is involved in the pathogenesis of kidney fibrosis as well as blood pressure control by regulating tubular sodium excretion. Long-term effects of ETA receptor blockade on blood pressure and kidney function in spontaneously hypertensive rats (SHRs) on a high-salt diet are unknown. We treated SHRs on a 6% (w/v) NaCl sodium diet (SHR-S) for 48 weeks with the ETA antagonist LU 135252 (whose selectivity for ETA is 150 times greater than for ETB) with 10, 30 and 100mg·kg-1·day-1 or placebo. The ETA antagonist had at no time-point any effect on blood pressure. Glomerular filtration rate was normal in SHR-S and not altered by LU 135252. However, urinary albumin excretion was markedly reduced by the ETA antagonist (SHR-S, 145±50mg/day; SHR-S+10mg·kg-1·day-1 LU 135252, 33±11mg/day, P<0.05 versus SHR-S; SHR-S+30mg·kg-1·day-1 LU 135252, 55±16mg/day and SHR-S+100mg·kg-1·day-1 LU 135252, 32±11mg/day, P<0.05 versus SHR-S at both concentrations). Total urinary protein excretion was likewise significantly reduced by treatment with 10mg·kg-1·day-1 LU 135252 (SHR-S, 0.25±0.06g/day; SHR-S+10mg·kg-1·day-1 LU 135252, 0.089±0.01g/day, P<0.05 versus SHR-S). The higher dosages of LU 135252 showed only a trend towards reduction of total urinary protein excretion. Computer-aided image analysis after haematoxylin/eosin and periodic acid-Schiff staining revealed that treatment with 10mg·kg-1·day-1 LU 135252 significantly reduces the media/lumen ratio of intrarenal arteries. Higher dosages of LU 135252 were less effective. Renal matrix protein synthesis in SHR-S was not altered by LU 135252. In conclusion, the renal ET system contributes in a blood-pressure-independent manner to the regulation of urinary protein excretion and renal vascular hypertrophy in SHR-S. Lower doses of the ETA antagonist were more effective, indicating that a potential additional blockade of the ETB receptor using higher doses of LU 135252 seems to oppose the beneficial effects of a sole ETA blockade. Urinary protein excretion is an independent risk factor of chronic renal failure, thus ETA antagonists might be a therapeutic tool to prevent proteinuria-induced chronic renal failure.

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.

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.

Office blood pressure is a predictor of aortic elastic properties and urinary protein excretion in subjects with white coat hypertension

2016 ◽  
Vol 203 ◽  
pp. 98-103 ◽  
Author(s):  
Konstantinos Aznaouridis ◽  
Charalambos Vlachopoulos ◽  
Konstantina Masoura ◽  
Panagiota Pietri ◽  
Gregory Vyssoulis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Elastic Properties ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Office Blood Pressure ◽  
White Coat ◽  
White Coat Hypertension ◽  
Protein Excretion ◽  
Aortic Elastic Properties

Primary versus secondary structural changes of the blood vessels in hypertension

1985 ◽  
Vol 63 (4) ◽  
pp. 392-401 ◽  
Author(s):  
Robert M. K. W. Lee ◽  
John S. Smeda
Keyword(s):  
Blood Pressure ◽  
Blood Vessels ◽  
Structural Changes ◽  
Vascular Wall ◽  
Wall Thickening ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Pressure Independent ◽  
Hypertension Development

Various researchers have hypothesized that the thickening of the vascular wall plays an important role in the maintenance of hypertension. Such an alteration can increase the vascular resistance by exerting two effects. A thickened vascular wall could occlude the lumen of the blood vessel and (or) cause the artery to hyperreact to contractile stimuli. Until recently, it has been a general conclusion that such alterations were a secondary adaptation produced by the elevation of blood pressure. Consistent with this view, certain classes of larger arteries do exhibit a thickened vascular wall late during hypertension development and such changes can be prevented from occurring by antihypertensive treatment. However, recent studies involving the mesenteric and renal arteries of Wistar-Kyoto spontaneously hypertensive rats have shown that wall thickening of the vasculature occurs prior to hypertension development and is present even under conditions where the blood pressure has been normalized throughout the animal's life. These latter observations suggest that some structural alterations in the blood vessels observed in hypertension are pressure independent and could be of etiological importance in the initiation of hypertension.

scholarly journals Organ Damage due to Elevation of Blood Pressure on NaCl-induced

2020 ◽  
Vol 3 (2) ◽  
pp. 108
Author(s):  
Hotimah Masdan Salim ◽  
Ilham Putra Alam ◽  
Widya Dio Kharisma
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Kidney Injury ◽  
Organ Damage ◽  
Left Ventricular ◽  
Increase Blood Pressure ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
Ventricular Relaxation

Introduction: High salt diet is known to induce or aggravate hypertension in hypertensive rats and humans. The elevation of blood pressure by NaCl-induced promotes cardiac hypertrophy, the impairment of left ventricular relaxation, endothelial dysfunction, and kidney injury. This study aimed to examine whether NaCl-induced caused increase blood pressure and weight of organs. Methods: Eight weeks old male Mus musculus were divided to two groups, one group was given NaCl 8% by intraperitoneal injection for 8 hours.Results: Blood pressure was measured previously, in this study systolic and diastolic blood pressure increased significantly (p < 0.05). The increasing of blood pressure was followed by significant increase in organ weight, such as heart and kidney (p < 0.05). Conclusion: This result suggested that NaCl-induced caused hypertension and increased organs weight that may cause early process of damages in organs.

Sign in / Sign up

Export Citation Format

Share Document