Faculty Opinions recommendation of Collecting duct renin is upregulated in both kidneys of 2-kidney, 1-clip goldblatt hypertensive rats.

1. Hyperinsulinaemia is considered to be a pathogenic factor for human and experimental hypertension. Thus, the contribution of the known insulin-stimulated tubular sodium reabsorption to this aetiological process has to be discussed. 2. Rats fed a fructose-enriched diet develop hyperinsulinaemia and hypertension, providing a model for studying the regulation of the tubular sodium handling and its possible relationship to hypertension. For this purpose, the sodium transport capacity of isolated nephron segments from control rats and from rats fed a fructose-enriched diet was investigated by measurement of ouabain-sensitive 86Rb uptake and of the hydrolytic activity of Na,K-ATPase. The number and affinity of insulin receptors were estimated from the specific [125I]insulin binding. 3. In rats fed a fructose-enriched diet, mild hypertension developed during the 14-day fructose diet. There were no differences, along the nephron, in basal 86Rb uptakes and ATPase activities between control rats and fructose-induced hypertensive rats. In control rats, insulin stimulated 86Rb uptake in the proximal convoluted tubule and cortical collecting duct, but exhibited an inhibitory action in the medullary thick ascending limb. In contrast, in fructose-induced hypertensive rats, 86Rb influx remained unresponsive to insulin concentrations ranging from 10−11 to 10−7 mol/l in the proximal convoluted tubule and cortical collecting duct. In the medullary thick ascending limb, the threshold of inhibition was displaced from 10−11 mol/l up to 10−7 mol/l. Insulin binding to the proximal convoluted tubule, medullary thick ascending limb and collecting duct were similar in control rats and in rats fed a fructose-enriched diet. 4. We conclude that hypertension developed in rats fed a fructose-enriched diet regardless of change in renal sodium handling since (1) the basal tubular sodium reabsorption capacity of the nephron remained unchanged and (2) the response of the tubular cation transport to insulin was abolished. These results strongly argue against the participation of insulin-mediated tubular sodium retention in the pathogenesis of hypertension and suggest that insulin-related mechanisms modulate the blood vessel reactivity.

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AT1 receptor-mediated enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats

AJP Renal Physiology ◽

10.1152/ajprenal.00462.2004 ◽

2005 ◽

Vol 289 (3) ◽

pp. F632-F637 ◽

Cited By ~ 93

Author(s):

Minolfa C. Prieto-Carrasquero ◽

Hiroyuki Kobori ◽

Yuri Ozawa ◽

Astrid Gutiérrez ◽

Dale Seth ◽

...

Keyword(s):

Angiotensin Ii ◽

Collecting Duct ◽

Receptor Activation ◽

Sodium Reabsorption ◽

Mrna Levels ◽

Ang Ii ◽

Distal Nephron ◽

Hypertensive Rats ◽

Kidney Medulla ◽

Collecting Ducts

Angiotensin II (ANG II)-infused rats exhibit increases in distal nephron renin expressed in principal cells of connecting tubules and collecting ducts. This study was performed to determine whether the augmentation of distal nephron renin involves ANG II type 1 (AT1) receptor activation. Male Sprague-Dawley rats (200–220 g) were divided into three groups: 1) sham operated ( n = 8); 2) ANG II infused (80 ng/min, 13 days, n = 8); and 3) ANG II infused plus AT1 receptor blocker (ARB), olmesartan (5 mg/days, n = 8). ANG II infusion increased systolic blood pressure (BP; 178 ± 4 vs. 122 ± 1 mmHg; P < 0.001) and suppressed plasma renin activity (PRA; 0.08 ± 0.1 vs. 5.3 ± 0.8 ng ANG I·ml−1·h−1). ARB treatment prevented the increase in BP (113 ± 6 mmHg) and led to increases in PRA (15.8 ± 1.5 ng ANG I·ml−1·h−1). Renin protein levels measured in the kidney medulla, to avoid contribution from juxtaglomerular appartus cells, were higher in ANG II-infused rats [1.64 ± 0.3 vs. 1.00 ± 0.1 densitometric units (DU) compared with sham-operated rats; P < 0.05], and ARB treatment prevented this increase (1.01 ± 0.1). Similarly, renin immunoreactivity increased in medullary collecting ducts of ANG II-infused compared with sham-operated rats (2.5 ± 0.3 vs. 1.0 ± 0.2 DU; P < 0.001), which was also prevented by ARB (1.01 ± 0.06). Renin qRTPCR in ANG II-infused rats showed higher mRNA levels in the kidney medulla compared with sham-operated rats (5.5 ± 2.3 vs. 0.04 ± 0.02 ratio to GAPDH mRNA levels; P < 0.001); however, renin transcript levels were normalized in the ARB-treated rats. These data demonstrate that the augmentation of distal nephron renin in ANG II-infused hypertensive rats is AT1 receptor mediated. The augmented distal tubular renin may contribute to increased intratubular ANG II levels and distal nephron sodium reabsorption in ANG II-dependent hypertension.

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Enhancement of Collecting Duct Renin in Angiotensin II–Dependent Hypertensive Rats

Hypertension ◽

10.1161/01.hyp.0000135678.20725.54 ◽

2004 ◽

Vol 44 (2) ◽

pp. 223-229 ◽

Cited By ~ 163

Author(s):

Minolfa C. Prieto-Carrasquero ◽

Lisa M. Harrison-Bernard ◽

Hiroyuki Kobori ◽

Yuri Ozawa ◽

Kathleen S. Hering-Smith ◽

...

Keyword(s):

Angiotensin Ii ◽

Collecting Duct ◽

Hypertensive Rats

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Oxygen availability limits renal NADPH-dependent superoxide production

AJP Renal Physiology ◽

10.1152/ajprenal.00115.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. F749-F753 ◽

Cited By ~ 56

Author(s):

Yifan Chen ◽

Pritmohinder S. Gill ◽

William J. Welch

Keyword(s):

Nadph Oxidase ◽

Cultured Cells ◽

Collecting Duct ◽

Rat Kidney ◽

Kidney Tissue ◽

Primary Source ◽

Renal Medulla ◽

Hypertensive Rats ◽

Enhanced Chemiluminescence ◽

Tissue Homogenates

Renal oxygen tension is substantially lower in the medulla than in the cortex and is reduced in hypertensive rats, a model of oxidative stress. Expression of NADPH oxidase, the primary source for superoxide anion (O2−·) in the kidney, is elevated in hypertension. Because molecular oxygen (O2) is required for O2−· formation, we tested the hypothesis that renal NADPH oxidase activity is limited by low O2. O2−· production by rat kidney tissue or cultured cells exposed to levels of Po2 that mimics those in the kidney was assessed by lucigenin-enhanced chemiluminescence. NADPH-dependent O2−· production by kidney homogenates decreased reversibly by 60–90% after graded reductions of ambient O2 from 10 to 0% (76 to 2 mmHg Po2). The NADPH-dependent O2−· production by the kidney homogenate was reduced by decreasing Po2 below ∼30 mmHg. The response of tissue homogenates to low Po2 was not different between normotensive and hypertensive rats. Similarly, NADPH-dependent O2−· production was lower during 2% O2 compared with 10% O2 in rat proximal tubule cells (−57 ± 1%), vascular smooth muscle (−42 ± 5%), cardiomyocytes (−57 ± 1%), and mouse inner medulla collecting duct cells (−58 ± 3%). We conclude that O2−· production by NADPH oxidase is dependent on availability of O2. Therefore, O2−· generation may be limited in the kidney, both in the normal renal medulla and in the cortex of hypertensive kidneys.

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Intranephron PGE2 production in stroke-prone spontaneously hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.258.4.h987 ◽

1990 ◽

Vol 258 (4) ◽

pp. H987-H993 ◽

Cited By ~ 1

Author(s):

F. Takemoto ◽

A. Miyanoshita ◽

K. Shimamura ◽

S. Sunano ◽

H. Endou

Keyword(s):

Spontaneously Hypertensive Rats ◽

Collecting Duct ◽

Pge2 Production ◽

Male Rats ◽

Ionophore A23187 ◽

Hypertensive Rats ◽

Adult Rats ◽

Spontaneously Hypertensive ◽

Wistar Kyoto ◽

Collecting Tubules

To investigate whether intranephron prostaglandin E2 (PGE2) production in stroke-prone spontaneously hypertensive rats (SHRSP) differs from that in Wistar-Kyoto rats (WKY), we measured PGE2 accumulation rates in microdissected nephron segments from 4- to 6- and 12- to 14-wk-old male rats by radioimmunoassay. In both young and adult WKY, PGE2 accumulation was highest in the papillary collecting duct (PCD) and outer medullary and cortical collecting tubules, intermediate in the glomerulus (Glm), medullary and cortical thick ascending limbs of Henle's loop, and distal tubule, and negligible in the proximal tubule. PGE2 accumulation in adult WKY was severalfold higher than that in young WKY. PGE2 accumulation in adult and prehypertensive young SHRSP was significantly lower than that of respective WKY in most segments, whereas urinary PGE2 excretion was significantly higher in SHRSP than in age-matched WKY. Plasma arginine vasopressin concentrations in adult SHRSP were significantly higher than in WKY. PGE2 accumulation stimulated by 5 microM arachidonic acid was significantly lower in SHRSP than in WKY in most segments of young rats but was lower only in Glm and PCD of adult rats. PGE2 accumulation stimulated by 2 microM Ca2+ ionophore A23187 was significantly lower in most segments of adult and young SHRSP. These results indicate that a decrease in renal tubular PGE2 productive activities in SHRSP might not be caused by secondary adaptation to hypertension.

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Soluble Form of the (Pro)Renin Receptor Is Augmented in the Collecting Duct and Urine of Chronic Angiotensin II–Dependent Hypertensive Rats

Hypertension ◽

10.1161/hypertensionaha.110.167957 ◽

2011 ◽

Vol 57 (4) ◽

pp. 859-864 ◽

Cited By ~ 97

Author(s):

Alexis A. Gonzalez ◽

Lucienne S. Lara ◽

Christina Luffman ◽

Dale M. Seth ◽

Minolfa C. Prieto

Keyword(s):

Angiotensin Ii ◽

Collecting Duct ◽

Soluble Form ◽

Hypertensive Rats

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Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive rats

AJP Renal Physiology ◽

10.1152/ajprenal.00413.2004 ◽

2005 ◽

Vol 289 (5) ◽

pp. F957-F968 ◽

Cited By ~ 34

Author(s):

Soo Wan Kim ◽

Weidong Wang ◽

Tae-Hwan Kwon ◽

Mark A. Knepper ◽

Jørgen Frøkiær ◽

...

Keyword(s):

Spontaneously Hypertensive Rats ◽

Water Retention ◽

Collecting Duct ◽

Tubular Dysfunction ◽

Renal Tubular Dysfunction ◽

Protein Abundance ◽

Hypertensive Rats ◽

Outer Medulla ◽

Spontaneously Hypertensive ◽

Medullary Collecting Duct

In models of genetic hypertension, renal tubular dysfunction could be involved in the increased sodium and water reabsorption. However, the molecular basis for the increased renal sodium and water retention remains largely undefined in spontaneously hypertensive rats (SHR). We hypothesized that dysregulation of renal epithelial sodium channels (ENaC), sodium (co)transporters, or aquaporin-2 (AQP2) could be involved in the pathogenesis of hypertension in SHR. Six-week-old or twelve-week-old SHR and corresponding age-matched Wistar-Kyoto control rats (WKY) were studied. In both SHR groups, systolic blood pressure was markedly increased, whereas urine output, creatinine clearance, and urinary sodium excretion were decreased compared with corresponding WKY. Moreover, urine osmolality and urine-to-plasma osmolality ratio were increased compared with WKY. Semiquantitative immunoblotting demonstrated that the protein abundance of β- and γ-subunits of ENaC was increased in the cortex and outer stripe of the outer medulla and inner stripe of the outer medulla (ISOM) in SHR, whereas α-ENaC abundance was increased in ISOM. Immunoperoxidase microscopy confirmed the increased labeling of β-ENaC and γ-ENaC subunits in the late distal convoluted tubule, connecting tubule, and cortical and outer medullary collecting duct segments. In contrast, subcellular localization of α-ENaC, β-ENaC, and γ-ENaC was not changed. Expression of sodium/hydrogen exchanger type 3, bumetanide-sensitive Na-K-2Cl cotransporter, and thiazide-sensitive Na-Cl cotransporter was not altered in SHR. AQP2 levels were increased in the ISOM in SHR, and immunoperoxidase microscopy demonstrated an increased apical labeling of AQP2 in the inner medullary collecting duct in SHR. These results suggest that the increased protein abundance of ENaC subunits as well as the increased apical targeting of AQP2 may contribute to renal sodium and water retention observed during the development of hypertension in SHR.

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