Differences in ouabain-induced natriuresis between isolated kidneys of Milan hypertensive and normotensive rats

1992 ◽  
Vol 82 (2) ◽  
pp. 185-190 ◽  
Author(s):  
Roland Foulkes ◽  
Romana G. Ferrario ◽  
Patricia Salvati ◽  
Giuseppe Bianchi
Keyword(s):  
Vascular Resistance ◽  
Receptor Occupancy ◽  
Renal Vascular Resistance ◽  
The Other ◽  
Hypertensive Rats ◽  
Other Hand ◽  
Before And After ◽  
Renal Vascular ◽  
Isolated Kidneys

1. Several observations support the hypothesis that in rats of the Milan hypertensive strain elevated levels of a circulating ouabain-like factor might normalize the elevated Na+ reabsorption, but, on the other hand, might contribute to the development of hypertension. 2. As the receptor occupancy of this endogenous factor seems to be reversible, the aim of our study was to test, in vitro, the hypothesis of its presence in isolated kidneys from Milan hypertensive rats by studying the response to exogenous ouabain before and after prolonged washing. 3. The kidneys were isolated from adult Milan hypertensive rats and from age-matched normotensive controls and ouabain was given at two different experimental time intervals: shortly (15 min) after washout or after a further 60 min of washout (75 min in total). Comparative experiments with the diuretic hydrochlorothiazide were performed using the same protocol. 4. Ouabain given after 15 min of perfusion caused an increase in renal vascular resistance, diuresis and natriuresis; these haemodynamic and tubular responses were similar in kidneys from both Milan hypertensive and Milan normotensive rats. If given after the washout period, ouabain caused a comparable increase in renal vascular resistance, but a significantly greater natriuresis in kidneys from Milan hypertensive rats as compared with kidneys from Milan normotensive rats. On the other hand, hydrochlorothiazide caused similar natriuresis in kidneys from both strains after washout. 5. These results support the hypothesis that a factor, capable of interacting with the ouabain receptor on the Na+/K+−ATPase of tubular cells, is present in the kidney of adult Milan hypertensive rats and that it can be removed by prolonged washout.

Renal Vascular Resistance in Spontaneously Hypertensive Rats

1971 ◽  
Vol 83 (1) ◽  
pp. 96-105 ◽  
Author(s):  
Björn Folkow ◽  
Margareta Hallbäck ◽  
Yen Lundgren ◽  
Lilian Weiss
Keyword(s):  
Vascular Resistance ◽  
Spontaneously Hypertensive Rats ◽  
Renal Vascular Resistance ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Renal Vascular

Reduced autoregulatory effectiveness in adenosine 1 receptor-deficient mice

2006 ◽  
Vol 290 (4) ◽  
pp. F888-F891 ◽  
Author(s):  
S. Hashimoto ◽  
Y. Huang ◽  
J. Briggs ◽  
J. Schnermann
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Blood Pressure Reduction ◽  
Renal Perfusion ◽  
Renal Vascular Resistance ◽  
Tubuloglomerular Feedback ◽  
Wild Type ◽  
Before And After ◽  
Renal Vascular ◽  
Deficient Mice

Adjustments of renal vascular resistance in response to changes in blood pressure are mediated by an interplay between the myocyte-inherent myogenic and the kidney-specific tubuloglomerular feedback (TGF) mechanisms. Using mice with deletion of the A1 adenosine receptor (A1AR) gene, we tested the prediction that the absence of TGF, previously established to result from A1AR deficiency, is associated with a reduction in the efficiency of autoregulation. In anesthetized wild-type (A1AR+/+) and A1AR-deficient mice (A1AR−/−), glomerular filtration rate (GFR) and renal blood flow (RBF) were determined before and after reducing renal perfusion pressure through a suprarenal aortic clamp. In response to a blood pressure reduction by 15.9 ± 1.34 mmHg in A1AR−/− ( n = 9) and by 14.2 ± 0.9 mmHg in A1AR+/+ mice ( n = 8; P = 0.31), GFR fell by 187.9 ± 37 μl/min and by 72.3 ± 10 μl/min in A1AR−/− and A1AR+/+ mice, respectively ( P = 0.013). Similarly, with pressure reductions of 14.8 ± 1.1 and 13.3 ± 1.5 mmHg in A1AR−/− ( n = 9) and wild-type mice ( n = 8), respectively ( P = 0.43), RBF fell by 0.17 ± 0.02 ml/min in A1AR−/− mice and by only 0.08 ± 0.02 ml/min in wild-type animals ( P = 0.0039). Autoregulatory indexes for both GFR and RBF were significantly higher in A1AR−/− compared with A1AR+/+ mice, indicating reduced regulatory responsiveness in the knockout animals. We conclude that autoregulation of renal vascular resistance is less complete in A1AR-deficient mice, an effect that is presumably related to absence of TGF regulation in these animals.

Effect of Nifedipine on Renal Haemodynamics in an Animal Model of Cyclosporin a Nephrotoxicity

1990 ◽  
Vol 79 (3) ◽  
pp. 259-266 ◽  
Author(s):  
P. G. McNally ◽  
F. Baker ◽  
N. Mistry ◽  
J. Walls ◽  
J. Feehally
Keyword(s):  
Cyclosporin A ◽  
Vascular Resistance ◽  
Filtration Rate ◽  
Spontaneously Hypertensive Rat ◽  
Renal Plasma Flow ◽  
Renal Haemodynamics ◽  
Renal Vascular Resistance ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Renal Vascular

1. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in the spontaneously hypertensive rat. 2. Cyclosporin A, administered daily by subcutaneous injection at 25 mg/kg body weight for 14 days, induced a significant reduction in glomerular filtration rate (35.3%) and effective renal plasma flow (45.0%), and an increase in renal vascular resistance (219%). Using this regimen, tubular, glomerular or vascular morphological damage was not evident on light microscopy. 3. The administration of nifedipine simultaneously with cyclosporin A from day 1 prevented the characteristic decline in renal function and increase in renal vascular resistance. However, the administration of nifedipine to spontaneously hypertensive rats previously exposed to cyclosporin A for 7 days failed to improve renal haemodynamics. 4. This study suggests that the beneficial effect conferred by nifedipine on cyclosporin A nephrotoxicity is present only when treatment is initiated simultaneously with cyclosporin A.

scholarly journals Analysis Of Candidate Genes Expected To Be Essential For Melanoma Surviving

2020 ◽  
Author(s):  
Irina Krivosheeva ◽  
Alexandra Filatova ◽  
Sergei Moshkovskii ◽  
Ancha Baranova ◽  
Mikhail Skoblov
Keyword(s):  
Cell Viability ◽  
Cell Line ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
Computational Models ◽  
Target Genes ◽  
The Other ◽  
Other Hand ◽  
Before And After

Abstract Cancers may be treated by selective targeting of the genes vital for their survival. A number of attempts have led to discovery of several genes essential for surviving of tumor cells of different types. In this work, we tried to analyze genes that were previously predicted to be essential for melanoma surviving. Here we present the results of transient siRNA-mediated knockdown of the four of such genes, namely, UNC45A, STK11IP, RHPN2 and ZNFX1, in melanoma cell line A375, then assayed the cells for their viability, proliferation and ability to migrate in vitro. In our study, the knockdown of the genes predicted as essential for melanoma survival does not lead to statistically significant changes in cell viability. On the other hand, for each of the studied genes, mobility assays showed that the knockdown of each of the target genes accelerates the speed of cells migrating. Possible explanation for such counterintuitive results may include insufficiency of the predicting computational models or the necessity of a multiplex knockdown of the genes.AimsTo examine the hypothesis of essentiality of hypomutated genes for melanoma surviving we have performed knockdown of several genes in melanoma cell line and analyzed cell viability and their ability to migrate.MethodsKnockdown was performed by siRNAs transfected by Metafectene PRO. The levels of mRNAs before and after knockdown were evaluated by RT-qPCR analysis. Cell viability and proliferation were assessed by MTT assay. Cell migration was assessed by wound healing assay.ResultsThe knockdown of the genes predicted as essential for melanoma survival does not lead to statistically significant changes in cell viability. On the other hand, for each of the studied genes, mobility assays showed that the knockdown of each of the target genes accelerates the speed of cells migrating. ConclusionOur results do not confirm initial hypothesis that the genes predicted essential for melanoma survival as a matter of fact support the survival of melanoma cells.

A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats

2008 ◽  
Vol 294 (6) ◽  
pp. R1847-R1855 ◽  
Author(s):  
Maarten P. Koeners ◽  
Branko Braam ◽  
Dionne M. van der Giezen ◽  
Roel Goldschmeding ◽  
Jaap A. Joles
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Renal Injury ◽  
Renal Vascular Resistance ◽  
Perinatal Exposure ◽  
Hypertensive Rats ◽  
No Donor ◽  
Renal Vascular

Enhancing perinatal nitric oxide (NO) availability persistently reduces blood pressure in spontaneously hypertensive rats. We hypothesize that this approach can be generalized to other models of genetic hypertension, for instance those associated with renal injury. Perinatal exposure to the NO donor molsidomine was studied in fawn-hooded hypertensive (FHH) rats, a model of mild hypertension, impaired preglomerular resistance, and progressive renal injury. Perinatal molsidomine increased urinary NO metabolite excretion at 8 wk of age, i.e., 4 wk after treatment was stopped ( P < 0.05). Systolic blood pressure was persistently reduced after molsidomine (42-wk females: 118 ± 3 vs. 141 ± 5 and 36-wk males: 139 ± 4 vs. 158 ± 4 mmHg; both P < 0.001). Perinatal treatment decreased glomerular filtration rate ( P < 0.05) and renal blood flow ( P < 0.01) and increased renal vascular resistance ( P < 0.05), without affecting filtration fraction, suggesting persistently increased preglomerular resistance. At 4 wk of age natriuresis was transiently increased by molsidomine ( P < 0.05). Molsidomine decreased glomerulosclerosis ( P < 0.05). Renal blood flow correlated positively with glomerulosclerosis in control ( P < 0.001) but not in perinatally treated FHH rats. NO dependency of renal vascular resistance was increased by perinatal molsidomine. Perinatal enhancement of NO availability can ameliorate development of hypertension and renal injury in FHH rats. Paradoxically, glomerular protection by perinatal exposure to the NO donor molsidomine may be due to persistently increased preglomerular resistance. The mechanisms by which increased perinatal NO availability can persistently reprogram kidney function and ameliorate hypertension deserve further study.

Impaired Autoregulatory Responses in Contralateral Kidneys of Two-Kidney, One-Clip Hypertensive Rats

1980 ◽  
Vol 59 (s6) ◽  
pp. 381s-384s ◽  
Author(s):  
D. W. Ploth ◽  
R. N. Roy ◽  
Wann-Chu Huang ◽  
L. G. Navar
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Urine Flow ◽  
Renal Vascular Resistance ◽  
Hypertensive Rats ◽  
Contralateral Kidney ◽  
Arterial Blood ◽  
Renal Vascular

1. Micropuncture and clearance experiments in two-kidney, one-clip renal vascular hypertensive rats examined the ability of the kidney contralateral to renal vascular stenosis to maintain renal function during conditions of reduced renal arterial blood pressure. 2. At their respective spontaneous blood pressures, renal vascular resistance was higher and glomerular filtration rate (GFR) and renal blood flow were not different in the contralateral kidneys of the hypertensive rats (170 ± 5 mmHg) compared with normal animals (129 ± 1 mmHg). Urine flow and absolute and fractional excretion of electrolyte were greater from the kidneys of the hypertensive animals. However, pressures in cortical structures were similar in the two groups. 3. As blood pressure was reduced acutely, the kidney contralateral to the renal artery stenosis achieved only small decreases in renal vascular resistance that failed to allow GFR, renal blood flow or pressures in cortical structures to be maintained. In contrast, normal rats efficiently autoregulated renal vascular resistance to allow GFR, renal blood flow and cortical pressures to be unchanged as blood pressure was altered between 130 and 115 mmHg. Urine flow and electrolyte excretion decreased to a greater extent in the hypertensive kidneys; at comparable blood pressure these indices of excretory function were not different in the two groups. 4. These observations indicate that the contralateral kidney can maintain normal haemodynamic and glomerular function only at elevated blood pressure and suggest the possibility that the impaired capacity to autoregulate renal resistances may contribute to the maintenance of hypertension observed in this model.

Renal vascular resistance and reactivity in the neurogenic hypertensive rat

1980 ◽  
Vol 239 (5) ◽  
pp. F474-F477 ◽  
Author(s):  
G. D. Fink ◽  
W. J. Bryan
Keyword(s):  
Vascular Resistance ◽  
Nervous Activity ◽  
Renal Vascular Resistance ◽  
Renal Nerves ◽  
Hypertensive Rats ◽  
Renal Nerve ◽  
Neurogenic Hypertension ◽  
Renal Vasoconstriction ◽  
Significant Difference ◽  
Renal Vascular

Increased sympathetic nervous system activity in the kidney has been postulated as a possible etiologic factor in some forms of hypertension. The present investigation sought to document the possibility of a chronic increase in neurogenic renal vasoconstriction in an experimental model in which increased nervous activity would be expected--neurogenic hypertension resulting from partial baroreceptor deafferentation. In anesthetized rats with chronic neurogenic hypertension, renal vascular resistance was significantly higher than in sham-operated rats. After acute renal denervation, there was no statistically significant difference in renal vascular resistance between the two groups. Thus, a chronic increase in neurogenic renal vascular resistance was apparent in the hypertensive rats. Since renal vascular responses to direct renal nerve activation, norepinephrine, and other exogenous vasoactive hormones were not altered in the hypertensive rats, the increased neurogenic vasoconstriction was probably the result of increased renal nerve discharge. Unaltered neurotransmission and reactivity further indicated a failure of the renal nerves or blood vessels to "adapt" to increased nervous activity. These results support previous suggestions that increased renal sympathetic nerve activity could result in sustained neurogenic renal vasoconstriction and thereby contribute to the development of hypertension.

Segmental renal vascular resistance in the spontaneously hypertensive rat

1982 ◽  
Vol 242 (6) ◽  
pp. H961-H966 ◽  
Author(s):  
C. H. Hsu ◽  
J. H. Slavicek ◽  
T. W. Kurtz
Keyword(s):  
Vascular Resistance ◽  
Spontaneously Hypertensive Rat ◽  
Renal Vascular Resistance ◽  
Hypertensive Rats ◽  
Mean Values ◽  
Spontaneously Hypertensive ◽  
Microsphere Method ◽  
Wistar Kyoto ◽  
Renal Vascular ◽  
Arteriolar Diameter

Renal hemodynamics were studied during different stages of development of hypertension in unanesthetized spontaneously hypertensive rats (SHR). In SHR at 4 wks of age mean arterial pressure (MAP) was higher than in age-matched Wistar Kyoto rats (WKY); however, renal blood flow (RBF) and renal vascular resistance (RVR) were not different between these two groups. Mean values of RVR and MAP in 8- and 12-wk-old SHR were significantly greater than those of age-matched WKY. Both RBF of 8- and 12-wk-old SHR were significantly lower than the corresponding values of WKY. Afferent arteriolar diameter (AAD) was measured with a microsphere method. AAD was not different between 4-wk-old SHR and WKY; however, the AAD of 8-wk-old (16.3 +/- 0.23 micrometers, n = 5) and 12-wk-old (17.4 +/- 0.48, n = 5) SHR were significantly smaller than those of respective control WKY (17.3 +/- 0.34, n = 4, P less than 0.05; 19.3 +/- 0.12, n = 5, P less than 0.01). Calculated preglomerular (Rpre) and postglomerular resistances (Rpost) of 12-wk-old SHR were increased 96 and 129% when compared with respective segmental resistances of the control WKY. The decrease in AAD of 12-wk-old SHR was sufficient to account for a 33% increase in Rpre. After the rats were treated with hydralazine (0.5 mg/kg iv), MAP, RBF, and RVR of SHR were not different from the control WKY values. Rpre and Rpost of SHR were substantially decreased; however, vasodilation occurred at vessels proximal and distal to the afferent arteriole because AAD was not altered. Our results indicate that increased RVR in SHR involves increases in Rpre and Rpost.

Effect of potassium on renal vascular resistance and urine flow rate

1959 ◽  
Vol 197 (2) ◽  
pp. 305-308 ◽  
Author(s):  
Jerry Scott ◽  
Dean Emanuel ◽  
Francis Haddy
Keyword(s):  
Blood Flow ◽  
Potassium Chloride ◽  
Vascular Resistance ◽  
Flow Rate ◽  
Blocking Agent ◽  
Urine Flow ◽  
Renal Vascular Resistance ◽  
Urine Flow Rate ◽  
Before And After ◽  
Renal Vascular

The effect of potassium chloride upon renal vascular resistance and urine flow rate was studied in anesthetized laparotomized dogs. Potassium chloride was infused directly into the renal artery with the rate of blood flow to the kidney held constant and with flow rate not controlled. Resistance progressively decreased when serum potassium level in the kidney was elevated by infusing 0.11–0.69 mEq K+/min. It progressively increased when the infusion rate exceeded 0.69 mEq/min. This relationship was unaltered by the adrenergic blocking agent phentolamine. Urine flow rate increased both before and after denervation of the kidney when potassium was infused at the rate of 0.6 mEq/min. This increase was not apparent when the rate of blood flow was held constant. These findings indicate that a local potassium excess in amounts which might occur naturally leads to dilatation of renal vessels and increase of urine flow rate. The latter probably is related to the former.

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