scholarly journals 3326 Radiofrequency Renal Denervation Prevents Further Progression of Hypertension and Decreases Renal Medullary Fibrosis in One-year-old Spontaneously Hypertensive Rats (SHR)

2019 ◽  
Vol 3 (s1) ◽  
pp. 19-19
Author(s):  
Juan Gao ◽  
Ian B Denys ◽  
Jane Sutphen ◽  
Luis Del Valle ◽  
Daniel R Kapusta
Keyword(s):  
Renal Fibrosis ◽  
Renal Denervation ◽  
Kidney Cortex ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Treatment Groups ◽  
Kidney Section ◽  
Study Population ◽  
Wistar Kyoto ◽  
One Year

OBJECTIVES/SPECIFIC AIMS: We have reported that radiofrequency renal denervation (RF-RDN) in SHR at 20-weeks of age, decreased blood pressure (BP) and fibrosis in kidney cortex and medulla when rats were sacrificed at 6 months. However, whether RF-RDN can have similar benefits in older rats remains unknown. This study examined whether performing RF-RDN in older rats also has a beneficial effect on BP and renal fibrosis. METHODS/STUDY POPULATION: Baseline systolic and diastolic BP (SBP/DPB) was measured (telemetry) in nine-month-old SHR and Wistar Kyoto rats (WKY). Groups of rats then received bilateral RF-RDN or Sham-RDN (SHR-RDN, n=9; SHR-Sham, n=10; WKY-RDN, n=5; WKY-Sham, n=8). Rats were then sacrificed at 12-months of age. Kidneys were harvested, sectioned, and assessed for fibrosis by Masson’s trichrome stain. A pathologist, who was blinded to treatment groups, evaluated each kidney section for fibrosis. RESULTS/ANTICIPATED RESULTS: Compared to SHR with Sham-RDN, RF-RDN prevented a further increase in systolic and diastolic BP from baseline (9-month) in SHR as they aged to 12-months (SHR-Sham mmHg: 9-month 193±4/127±4; 12-month 207±3/142±5; SHR-RDN mmHg: 9-month 197±3/132±2; 12-month 197±4/132±3). RF-RDN did not alter SBP or DBP in aged WKY. One-year-old SHR with prior Sham-RDN showed extensive renal fibrosis in kidney cortex and medulla. In contrast, RF-RDN significantly decreased renal fibrosis in the medulla, but not cortex. There was no fibrosis in kidneys of age matched WKY. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that RF-RDN may be a potential therapy for halting progression of hypertension and decreasing medullary fibrosis in the aged population.

Role of renal nerves in onset and maintenance of spontaneous hypertension

1982 ◽  
Vol 243 (2) ◽  
pp. H284-H288 ◽  
Author(s):  
R. A. Norman ◽  
D. J. Dzielak
Keyword(s):  
Arterial Pressure ◽  
Renal Denervation ◽  
Indirect Measurement ◽  
Renal Nerves ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Norepinephrine Content ◽  
Wistar Kyoto

Renal denervation has been reported to delay development of hypertension in Okamoto spontaneously hypertensive rats (SHR) but to have no effect on the final hypertensive state. However, functional reinnervation begins to occur about 1 mo after renal denervation. The arterial pressure of SHR undergoing repeated bilateral renal denervations at the age of 4, 7, 10, 13, and 16 wk was compared with that in sham-operated SHR. In addition, the effect of successive renal denervations at 4, 7, and 10 wk of age in Wistar-Kyoto (WKY) control rats was determined. Both indirect measurement of pressure by the tail-cuff technique and mean arterial pressure (MAP) measurement indicated that renal denervation prevents full expression of hypertension in SHR. MAP in 19-wk-old renal-denervation SHR averaged 159 +/- 5.1 mmHg (SE) vs. 178 +/-0 4.2 mmHg in sham-operated SHR. Renal denervation had no effect on arterial pressure of WKY rats. Renal norepinephrine content in the renal-denervated WKY rats and SHR was less than 20% of that in the sham-operated groups. Successive bilateral renal denervations every 3 wk blocks 30-40% of the expected progressive elevation of arterial pressure in aging SHR.

scholarly journals 2267 Radiofrequency renal denervation attenuates kidney fibrosis in spontaneously hypertensive rats

2018 ◽  
Vol 2 (S1) ◽  
pp. 25-25
Author(s):  
Juan Gao ◽  
Ian B. Denys ◽  
Luis Del Valle ◽  
Mihran V. Naljayan ◽  
Daniel R. Kapusta
Keyword(s):  
T Cells ◽  
Renal Fibrosis ◽  
Kidney Tissue ◽  
Kidney Cortex ◽  
Kidney Fibrosis ◽  
Spontaneously Hypertensive ◽  
Tnf Α ◽  
Study Population ◽  
Bowman's Capsule ◽  
Renal Sympathetic

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to investigate whether RF-RDN attenuates renal fibrosis and inflammation in SHR with established hypertension. METHODS/STUDY POPULATION: Twenty-two-week-old SHR received bilateral RF-RDN or Sham-RDN (Biosense Webster Stockert 70 generator and RF-probe). Four weeks later, SHR were sacrificed and paraffin sections of kidneys were stained for fibrosis by Masson’s trichrome staining. Kidney tissue were homogenized for measurement of cytokines levels by ELISA. RESULTS/ANTICIPATED RESULTS: The results showed that Sham-RDN treated SHR had extensive fibrosis as demonstrated by moderate thickening of Bowman’s capsule, collagen deposition in glomerulus, extensive tubulointerstitial fibrosis, and segmental glomerulosclerosis. In contrast, RF-RDN significantly reduced each of these pathological components of fibrosis in kidney cortex and medulla as compared with Sham-RDN treated kidneys. In other studies, RF-RDN decreased B cells, CD4+ T cells, and CD8+ T cells in the kidney of SHR as measured by flow cytometry. Meanwhile, kidney tissue levels of IL-17, INF-γ, MIP-3a, TNF-α, and TGF-β were decreased as compared with respective levels in Sham-RDN. DISCUSSION/SIGNIFICANCE OF IMPACT: Together, these findings demonstrate that removal of the influence of heightened renal sympathetic activity by RF-RDN decreases kidney inflammatory markers and attenuates renal fibrosis in hypertensive SHR.

Alteration in sialidase and other glycosidase activities in the kidney of spontaneously hypertensive rats: persistence after preventive treatment with hydralazine

1988 ◽  
Vol 66 (7) ◽  
pp. 884-888 ◽  
Author(s):  
L. Cohen-Forterre ◽  
A. M. Grigorova-Borsos ◽  
C. Falcy ◽  
G. Mansour ◽  
G. Mozere ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Enzyme Activities ◽  
Spontaneously Hypertensive Rats ◽  
Specific Activity ◽  
Blood Pressure Level ◽  
Preventive Treatment ◽  
Kidney Cortex ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Because kidney microangiopathy with capillary basement membrane thickening has been reported in spontaneous hypertension, we have studied the activities of three lysosomal glycosidases able to degrade the carbohydrate moieties of basement membrane constituents in the kidney cortex of 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). These activities were also determined in SHR and WKY treated from 6 to 12 weeks of age with hydralazine (mean dose, 18 mg/kg per day in drinking water). Sialidase specific activity on sialyl-α2-3-[3H]lactitol was markedly decreased in the kidney of untreated SHR, 40% activity remaining relative to that found in untreated age-matched WKY (p < 0.001). β-Galactosidase specific activity on p-nitrophenyl-β-D-galactoside was also decreased, 86% activity remaining relative to that found in untreated WKY (p < 0.001). Glucosyl-galactosyl-hydroxylysyl glucohydrolase specific activity on glucosyl-galactosyl-hydroxylysine was equally diminished, 74% activity remaining relative to that found in untreated age-matched WKY (p < 0.001). In contrast, the activities of two control glycosidases inactive on the carbohydrate moieties of basement membrane constituents, α-glucosidase assayed with p-nitrophenyl-α-D-glucoside as substrate and β-glucosidase assayed with p-nitrophenyl-β-D-glucoside as substrate, were significantly increased. All the alterations in enzyme activities observed in the kidney of SHR were also present in the long-term treated normotensive SHR. No effect of the hydralazine treatment on the three enzyme activities investigated could be demonstrated in the WKY. Thus the alterations observed in the kidneys of SHR appear to be independent of blood pressure level.

Role of renal nerves on pressure natriuresis in spontaneously hypertensive rats

1991 ◽  
Vol 260 (1) ◽  
pp. F81-F85 ◽  
Author(s):  
M. Yoshida ◽  
S. Satoh
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Renal Denervation ◽  
Plasma Renin ◽  
Renal Nerves ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Rightward Shift ◽  
Fractional Excretion Of Sodium ◽  
Wistar Kyoto ◽  
Pressure Natriuresis

An abnormal rightward shift of the pressure-natriuresis curve is a well known feature of the renal function in hypertension. The participation of intrinsic neural factors in the kidney in this phenomenon was investigated in anesthetized young and adult spontaneously hypertensive rats (SHR). At 7-8 wk of age, the renal pressure-diuresis curve and pressure-natriuresis curve were shifted to the left in denervated SHR compared with innervated animals. Fractional excretion of sodium was higher, and plasma renin activity was lower in denervated SHR. Glomerular filtration rate was not affected by renal denervation. In 13- to 15-wk-old SHR, renal denervation did not affect the pressure-diuresis and -natriuresis curves, although other parameters were changed compared with the results at 7-8 wk. In Wistar-Kyoto rats, the pressure-diuresis curve was shifted to the left by renal denervation at both ages. These results suggest that the renal nerves have an important effect on the renal pressure-diuresis and -natriuresis curves. However, renal innervation cannot be thought to cause an abnormal rightward shift of the pressure-diuresis and -natriuresis curves in SHR, especially in the established stage of hypertension.

Increased transport of inorganic phosphate in renal brush borders of spontaneously hypertensive rats

1986 ◽  
Vol 250 (3) ◽  
pp. F470-F475 ◽  
Author(s):  
R. J. Bindels ◽  
J. A. Geertsen ◽  
C. H. Van Os
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Membrane Vesicles ◽  
Phosphate Transport ◽  
Serum Phosphate ◽  
Kidney Cortex ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Renal Brush Border Membrane ◽  
Transport Of Inorganic Phosphate ◽  
Wistar Kyoto

Phosphate metabolism was studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) by measuring serum phosphate concentrations and 24-h urinary phosphate excretions in rats placed in metabolic cages from 6 to 23 wk of age. Serum phosphate concentrations in SHR were significantly lower than those in WKY at 6, 12, and 20 wk of age. In addition, 24-h urinary phosphate excretion was lower in SHR relative to WKY from 6 through 23 wk of age. The hypophosphaturia in SHR was accompanied with an increase in the maximal transport rate of Na+-dependent phosphate transport in renal brush border membrane vesicles (BBMV) isolated from kidney cortex at 6, 12, and 20 wk of age. The apparent affinity for phosphate did not differ significantly between WKY and SHR at all ages studied. A direct relationship between maximal Na+-dependent phosphate transport rates in BBMV and serum phosphate concentrations was observed in both strains. In SHR, phosphate homeostasis is disturbed from 6 wk of age on.

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