Interactions between nitric oxide and renal nerves in the excretion of a saline load in obese Zucker rats

2001 ◽  
Vol 101 (3) ◽  
pp. 275-283 ◽  
Author(s):  
Orawan WONGMEKIAT ◽  
Edward J. JOHNS
Keyword(s):  
Nitric Oxide ◽  
Sympathetic Nerves ◽  
Urinary Sodium Excretion ◽  
No Synthase ◽  
Zucker Rats ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Renal Innervation

The present study investigated the potential role of nitric oxide (NO) and its interaction with renal sympathetic nerves in modulating the excretory responses to an acute saline volume expansion (VE), of 10% of body weight, in the innervated and denervated kidneys of both lean and obese Zucker rats. This was done using the NO synthase inhibitors NG-nitro-l-arginine methyl ester (l-NAME), 7-nitroindazole and aminoguanidine. In lean rats, cumulative urinary sodium excretion (cuUNaV) after 40 min of VE in the innervated kidney was enhanced by 48% in l-NAME-treated rats compared with that in untreated rats, but this was not the case for the denervated kidney. VE in untreated obese rats raised cuUNaV to a lesser extent than in the untreated lean rats, by 36% and 46% in the denervated and innervated kidneys respectively (both P < 0.001). l-NAME treatment of obese rats increased cuUNaV after VE compared with that in untreated obese rats, by 48% in the denervated kidney and by 136% in the innervated kidney (both P < 0.001). The magnitude of cuUNaV after VE in both kidneys of 7-nitroindazole-treated obese rats was not different from that in untreated obese rats. However, cuUNaV was raised (P < 0.01) by 56% in the innervated, but not the denervated, kidney of aminoguanidine-treated obese rats. These data show that NO is partially involved in mediating the reflex renal responses to VE in Zucker rat strains. NO, possibly generated by endothelial NO synthase, exerts its effects in obese rats through a renal-nerve-independent mechanism, while the effect of NO generated by inducible NO synthase requires intact renal innervation.

scholarly journals Renoprotection Induced by Aerobic Training Is Dependent on Nitric Oxide Bioavailability in Obese Zucker Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Rodrigo Vanerson Passos Neves ◽  
Hugo de Luca Corrêa ◽  
Ivo Vieira de Sousa Neto ◽  
Michel Kendy Souza ◽  
Fernando Costa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Aerobic Training ◽  
Redox Balance ◽  
Zucker Rats ◽  
Vasoactive Peptides ◽  
Renal Histology ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Inflammatory Profile ◽  
Nonpharmacological Intervention

Aerobic training (AT) promotes several health benefits that may attenuate the progression of obesity associated diabetes. Since AT is an important nitric oxide (NO-) inducer mediating kidney-healthy phenotype, the present study is aimed at investigating the effects of AT on metabolic parameters, morphological, redox balance, inflammatory profile, and vasoactive peptides in the kidney of obese-diabetic Zucker rats receiving L-NAME (N(omega)-nitro-L-arginine methyl ester). Forty male Zucker rats (6 wk old) were assigned into four groups ( n = 10 , each): sedentary lean rats (CTL-Lean), sedentary obese rats (CTL-Obese), AT trained obese rats without blocking nitric oxide synthase (NOS) (Obese+AT), and obese-trained with NOS block (Obese+AT+L-NAME). AT groups ran 60 min in the maximal lactate steady state (MLSS), five days/wk/8 wk. Obese+AT rats improved glycemic homeostasis, SBP, aerobic capacity, renal mitochondria integrity, redox balance, inflammatory profile (e.g., TNF-α, CRP, IL-10, IL-4, and IL-17a), and molecules related to renal NO- metabolism (klotho/FGF23 axis, vasoactive peptides, renal histology, and reduced proteinuria). However, none of these positive outcomes were observed in CTL-Obese and Obese+AT+L-NAME ( p < 0.0001 ) groups. Although Obese+AT+L-NAME lowered BP (compared with CTL-Obese; p < 0.0001 ), renal damage was observed after AT intervention. Furthermore, AT training under conditions of low NO- concentration increased signaling pathways associated with ACE-2/ANG1-7/MASr. We conclude that AT represents an important nonpharmacological intervention to improve kidney function in obese Zucker rats. However, these renal and metabolic benefits promoted by AT are dependent on NO- bioavailability and its underlying regulatory mechanisms.

Obesity lowers hyperglycemic threshold for impaired in vivo endothelial nitric oxide function

2002 ◽  
Vol 283 (1) ◽  
pp. H391-H397 ◽  
Author(s):  
H. G. Bohlen ◽  
Geoffrey P. Nase
Keyword(s):  
Nitric Oxide ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Zucker Rats ◽  
Kinase C ◽  
Lower Glucose ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Endothelial Nitric Oxide

Obesity is a risk for type II diabetes mellitus and increased vascular resistance. Disturbances of nitric oxide (NO) physiology occur in both obese animals and humans. In obese Zucker rats, we determined whether a protein kinase C-βII (PKC-βII) mechanism may lower the resting NO concentration ([NO]) and predispose endothelial NO abnormalities at lower glucose concentrations than occur in lean rats. NO was measured with microelectrodes touching in vivo intestinal arterioles. At rest, the [NO] in obese Zucker rats was 60 nm less than normal or about a 15% decline. After local blockade of PKC-βII with LY-333531, the [NO] increased ∼90 nm in obese rats but did not change in lean rats. In lean rats, administration of 300 mg/dl d-glucose for 45 min depressed endothelium-dependent dilation; only 200 mg/dl was required in obese animals. These various observations indicate that resting [NO] is depressed in obese rats by a PKC-βII mechanism and the hyperglycemic threshold for endothelial NO suppression is reduced to 200 mg/dl d-glucose.

Nitric oxide and renal nerve-mediated proximal tubular reabsorption in normotensive and hypertensive rats

1999 ◽  
Vol 277 (4) ◽  
pp. F560-F566 ◽  
Author(s):  
Xiao Chun Wu ◽  
Peter J. Harris ◽  
Edward J. Johns
Keyword(s):  
Nitric Oxide ◽  
Wistar Rats ◽  
Epithelial Transport ◽  
Sympathetic Nerves ◽  
Hypertensive Rats ◽  
Renal Nerve ◽  
Spontaneously Hypertensive ◽  
Fluid Uptake ◽  
Proximal Tubular ◽  
Renal Innervation

In Inactin-anesthetized Wistar rats with an intact renal innervation, intratubular nitro-l-arginine methyl ester (l-NAME, 10−4 M) increased proximal fluid uptake ( J va, at 2.47 ± 0.61 × 10−4mm3 ⋅ mm−2 ⋅ s−1) by 17% ( P < 0.05), whereas coadministration with sodium nitroprusside (SNP, 10−4 M) decreased J va by 18% ( P < 0.01). Similar manipulation of NO generation was without effect in groups of Wistar rats subjected to acute renal denervation. Intratubular aminoguanidine (10−4 M), a selective inducible nitric oxide synthase (NOS) blocker, had no effect on J va in intact kidneys of Wistar rats, but the neuronal NOS (nNOS) blocker, 7-nitroindazole (10−4 M and 10−6 M) increased J va by 19–23% (both P < 0.001). In stroke-prone spontaneously hypertensive rats (SHRSP), J va values in the innervated kidneys were lower ( P< 0.05) than in the corresponding Wistar groups and were unchanged by intratubular l-NAME or l-NAME plus SNP. The tonic attenuation of proximal epithelial transport by NO was dependent on the renal sympathetic nerves and appeared to be generated by the nNOS isoform of the enzyme. This role of NO was not evident in the SHRSP.

Modulation of noradrenaline-induced vasoconstriction in isolated perfused mesenteric arterial beds from obese Zucker rats in the presence and absence of insulin

2002 ◽  
Vol 80 (3) ◽  
pp. 171-179 ◽  
Author(s):  
Yi He ◽  
Kathleen M MacLeod
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Receptor Antagonist ◽  
Vascular Reactivity ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Significant Difference ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Presence And Absence

The genetically obese Zucker rat (fa/fa) is an insulin-resistant animal model with early-onset severe hyperinsulinemia that eventually develops mild hypertension. Thus, it represents a model in which the effect of hyperinsulinemia – insulin resistance associated with hypertension on vascular reactivity can be examined. The purpose of this study was to investigate the contribution of endogenous nitric oxide (NO) and prostaglandins to reactivity to noradrenaline (NA) in the presence and absence of insulin in mesenteric arterial beds (MAB) from 25-week-old obese Zucker rats and their lean, gender-matched littermates. In the absence of insulin, bolus injection of NA (0.9–90 nmol) produced a dose-dependent increase in perfusion pressure in MAB from both lean and obese rats. Although there was no significant difference in NA pD2 (–log ED50) values, the maximum response of MAB from obese rats to NA was slightly but significantly reduced compared with that of MAB from lean rats. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 300 µM) enhanced and indomethacin (20 µM) inhibited pressor responses to NA in MAB from both obese and lean rats. Perfusion with insulin (200 mU/L, a level similar to that in obese rats in vivo) potentiated only the responses of the obese MAB to the two lowest doses of NA tested (0.9 and 3 nmol). In the presence of L-NMMA, insulin further potentiated the NA response in MAB from obese rats. Indomethacin, the prostaglandin H2/thromboxane A2 receptor antagonist SQ 29548 (0.3 µM), and the nonselective endothelin-1 (ET-1) receptor antagonist bosentan (3 µM) all abolished insulin potentiation of the NA response in obese MAB. These data suggest that concurrent release of NO and vasoconstrictor cyclooxygenase product(s) in MAB from both obese and lean Zucker rats normally regulates NA-induced vasoconstrictor responses. Furthermore, insulin increases the release of contracting cyclooxygenase product(s) and enhances reactivity to low doses of NA in MAB from obese rats. The effects of insulin may be partially mediated by ET-1 via ET receptors and are buffered to some extent by concomitant NO release. This altered action of insulin may play a role in hypertension in this hyperinsulinemic – insulin-resistant model.Key words: hyperinsulinemia, insulin resistance, hypertensive Zucker obese rat, mesenteric arterial bed, noradrenaline.

Enhanced AT1 receptor-mediated vasocontractile response to ANG II in endothelium-denuded aorta of obese Zucker rats

2007 ◽  
Vol 292 (4) ◽  
pp. H1722-H1727 ◽  
Author(s):  
Athar H. Siddiqui ◽  
Tahir Hussain
Keyword(s):  
Isometric Tension ◽  
No Synthase ◽  
Receptor Protein ◽  
Zucker Rats ◽  
No Production ◽  
Ang Ii ◽  
No Donor ◽  
Obese Rats ◽  
Obese Zucker Rats

In the present study, we tested the hypothesis that ANG II causes a greater vasoconstriction in obese Zucker rats, a model of type 2 diabetes, with mild hypertension. Measurement of isometric tension in isolated aortic rings with intact endothelium revealed a modest but not significantly greater ANG II-induced contraction in obese than lean rats. Removal of endothelium or inhibition of nitric oxide (NO) synthase by NG-nitro-l-arginine methyl ester (l-NAME) enhanced 1) ANG II-induced contraction in both lean and obese rats, being significantly greater in obese rats (Emax g/g tissue, denuded: lean 572 ± 40 vs. obese 664 ± 16; l-NAME: lean 535 ± 14 vs. obese 818 ± 23) and 2) ANG II sensitivity in obese compared with lean rats, as revealed by the pD2 values. Endothelin-1 and KCl elicited similar contractions in the aortic rings of lean and obese rats. ACh, a NO-dependent relaxing hormone, produced greater relaxation in the aortic rings of obese than lean rats, whereas sodium nitroprusside, an NO donor, elicited similar relaxations in both rat strains. The expression of the ANG type 1 (AT1) receptor protein and mRNA in the endothelium-intact aorta was significantly greater in obese than lean rats, whereas the endothelium-denuded rings expressed modest but not significantly greater levels of AT1 receptors in obese than lean rats. The endothelial NO synthase protein and mRNA expression levels were higher in the aorta of obese than lean animals. We conclude that, although ANG II produces greater vasoconstriction in obese rat aortic rings, enhanced endothelial AT1 receptor-mediated NO production appears to counteract the increased ANG II-induced vasoconstriction, suggesting that arterial AT1 receptor may not be a contributing factor to hypertension in this model of obesity.

scholarly journals Role of Neural NO Synthase (nNOS) Uncoupling in the Dysfunctional Nitrergic Vasorelaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e36027 ◽  
Author(s):  
Ana Sánchez ◽  
Cristina Contreras ◽  
María Pilar Martínez ◽  
Belén Climent ◽  
Sara Benedito ◽  
...  
Keyword(s):  
No Synthase ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Obese Zucker Rats ◽  
Penile Arteries

scholarly journals High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT2R-MasR axis in obese Zucker rats

2012 ◽  
Vol 303 (3) ◽  
pp. F412-F419 ◽  
Author(s):  
Preethi Samuel ◽  
Quaisar Ali ◽  
Rifat Sabuhi ◽  
Yonnie Wu ◽  
Tahir Hussain
Keyword(s):  
Sodium Intake ◽  
Zucker Rats ◽  
Kidney Cortex ◽  
Complex Nature ◽  
Ang Ii ◽  
Pronounced Increase ◽  
High Sodium ◽  
High Sodium Intake ◽  
Obese Rats ◽  
Obese Zucker Rats

High sodium intake is known to regulate the renal renin-angiotensin system (RAS) and is a risk factor for the pathogenesis of obesity-related hypertension. The complex nature of the RAS reveals that its various components may have opposing effects on natriuresis and blood pressure regulation. We hypothesized that high sodium intake differentially regulates and shifts a balance between opposing components of the renal RAS, namely, angiotensin-converting enzyme (ACE)-ANG II-type 1 ANG II receptor (AT1R) vs. AT2-ACE2-angiotensinogen (Ang) (1–7)-Mas receptor (MasR), in obesity. In the present study, we evaluated protein and/or mRNA expression of angiotensinogen, renin, AT1A/BR, ACE, AT2R, ACE2, and MasR in the kidney cortex following 2 wk of a 8% high-sodium (HS) diet in lean and obese Zucker rats. The expression data showed that the relative expression pattern of ACE and AT1BR increased, renin decreased, and ACE2, AT2R, and MasR remained unaltered in HS-fed lean rats. On the other hand, HS intake in obese rats caused an increase in the cortical expression of ACE, a decrease in ACE2, AT2R, and MasR, and no changes in renin and AT1R. The cortical levels of ANG II increased by threefold in obese rats on HS compared with obese rats on normal salt (NS), which was not different than in lean rats. The HS intake elevated mean arterial pressure in obese rats (27 mmHg) more than in lean rats (16 mmHg). This study suggests that HS intake causes a pronounced increase in ANG II levels and a reduction in the expression of the ACE2-AT2R-MasR axis in the kidney cortex of obese rats. We conclude that such changes may lead to the potentially unopposed function of AT1R, with its various cellular and physiological roles, including the contribution to the pathogenesis of obesity-related hypertension.

scholarly journals Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats

2005 ◽  
Vol 153 (6) ◽  
pp. 963-969 ◽  
Author(s):  
Dorte X Gram ◽  
Anker J Hansen ◽  
Michael Wilken ◽  
Torben Elm ◽  
Ove Svendsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Sensory Nerve ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Nerve Activity ◽  
Calcitonin Gene ◽  
Obese Rats ◽  
Obese Zucker Rats

Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity – and therefore might be involved in the pathophysiology – is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin. Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1±3.4 pmol/l in pre-obese Zucker rats vs 6.9±1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3±0.2 mmol/l vs 5.1±0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8±0.3 mmol/l vs 8.6±0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver. Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.

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