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.

scholarly journals Caveolin-1/Endothelial Nitric Oxide Synthase Interaction Is Reduced in Arteries From Pregnant Spontaneously Hypertensive Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Jéssica A. Troiano ◽  
Simone R. Potje ◽  
Murilo E. Graton ◽  
Emily T. Gonçalves ◽  
Rita C. Tostes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wistar Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Caveolin 1 ◽  
Vascular Bed ◽  
Hsp90 Expression ◽  
Mesenteric Vascular Bed ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We have investigated the role caveolae/caveolin-1 (Cav-1) plays in endothelial nitric oxide synthase (eNOS) activation and how it impacts pregnancy-induced decreased vascular reactivity in normotensive (Wistar rats) and spontaneously hypertensive rats (SHR). Wistar rats and SHR were divided into non-pregnant (NP) and pregnant (P). Nitrite levels were assessed by the Griess method in the aorta and mesenteric vascular bed. In functional studies, arteries were incubated with methyl-β-cyclodextrin (dextrin, 10mmol/L), which disrupts caveolae by depleting cholesterol, and concentration-response curves to phenylephrine (PE) and acetylcholine (ACh) were constructed. Electronic microscopy was used to determine endothelial caveolae density in the aorta and resistance mesenteric artery in the presence of vehicle or dextrin (10mmol/L). Western blot was performed to evaluate Cav-1, p-Cav-1, calmodulin (CaM), and heat shock protein 90 (Hsp90) expression. Cav-1/eNOS interaction in the aorta and mesenteric vascular bed was assessed by co-immunoprecipitation. Nitric oxide (NO) generation was greater in arteries from P groups compared to NP groups. Dextrin did not change vascular responses in the aorta from P groups or the number of caveolae in P groups compared to NP groups. Compared to NP Wistar rats, NP SHR showed smaller number of caveolae and reduced Cav-1 expression. Pregnancy did not alter Cav-1, CaM, or Hsp90 expression in the aorta or mesenteric vascular bed from Wistar rats or SHR. These results suggest that pregnancy does not alter expression of the main eNOS regulatory proteins, but it decreases Cav-1/eNOS interaction. Reduced Cav-1/eNOS interaction in the aorta and mesenteric vascular bed seems to be an important mechanism to increase eNOS activity and nitric oxide production in pregnant normotensive and hypertensive rats.

Defective nitric oxide production impairs angiotensin II-induced Na-K-ATPase regulation in spontaneously hypertensive rats

2012 ◽  
Vol 302 (1) ◽  
pp. F47-F51 ◽  
Author(s):  
Apurva A. Javkhedkar ◽  
Mustafa F. Lokhandwala ◽  
Anees Ahmed Banday
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
High Concentration ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Proximal Tubular ◽  
Stimulation Of

Angiotensin (ANG) II via ANG II type 1 receptors (AT1R) activates renal sodium transporters including Na-K-ATPase and regulates sodium homeostasis and blood pressure. It is reported that at a high concentration, ANG II either inhibits or fails to stimulate Na-K-ATPase. However, the mechanisms for these phenomena are not clear. Here, we identified the signaling molecules involved in regulation of renal proximal tubular Na-K-ATPase at high ANG II concentrations. Proximal tubules from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were incubated with low concentrations of ANG II (pM), which activated Na-K-ATPase in both the groups; however, the stimulation was more robust in SHR. A high concentration of ANG II (μM) failed to stimulate Na-K-ATPase in WKY rats. However, in SHR ANG II (μM) continued to stimulate Na-K-ATPase, which was sensitive to the AT1R antagonist candesartan. In the presence of NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthase (NOS) inhibitor, ANG II (μM) caused stimulation of Na-K-ATPase in proximal tubules of WKY rats while having no further stimulatory effect in SHR. ANG II (μM), via AT1R, increased proximal tubular NO levels in WKY rats but not in SHR. In SHR, NOS was uncoupled as incubation of proximal tubules with ANG II and l-arginine, a NOS substrate, caused superoxide generation only in SHR and not in WKY rats. The superoxide production in SHR was sensitive to l-NAME. There was exaggerated proximal tubular AT1R-G protein coupling and NAD(P)H oxidase activation in response to ANG II (μM) in proximal tubules of SHR compared with WKY rats. In SHR, inhibition of NADPH oxidase restored NOS coupling and ANG II-induced NO accumulation. In conclusion, at a high concentration ANG II (μM) activates renal NO signaling, which prevents stimulation of Na-K-ATPase in WKY rats. However, in SHR ANG II (μM) overstimulates NADPH oxidase, which impairs the NO system and leads to continued Na-K-ATPase activation.

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.

Impaired effect of nitric oxide synthesis inhibition on tubuloglomerular feedback in hypertensive rats

1996 ◽  
Vol 271 (2) ◽  
pp. F246-F252 ◽  
Author(s):  
C. Thorup ◽  
A. E. Persson
Keyword(s):  
Nitric Oxide ◽  
Flow Rate ◽  
Turning Point ◽  
Tubuloglomerular Feedback ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Proximal Tubular ◽  
Flow Pressure ◽  
Wistar Kyoto ◽  
Stop Flow

Experiments were conducted to compare the effects of intratubular inhibition [N omega-nitro-L-arginine (L-NNA)] of nitric oxide (NO) on the tubuloglomerular feedback (TGF) mechanism between anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and between the Milan hypertensive (MHS) and the Milan normotensive (MNS) strains of rats. Changes in proximal tubular stop-flow pressure (Psf) in response to various loop of Henle perfusion rates and measurements of early proximal flow rate (EPFR) were used to characterize TGF. Maximal drop in Psf (delta Psf) were used to indicate TGF reactivity and the flow rate eliciting half-maximal delta Psf (turning point; TP) to indicate TGF sensitivity. Under control conditions, TGF sensitivity was significantly higher in SHR than in WKY, but, after L-NNA infusion, TP was decreased in WKY and not in SHR. L-NNA infusion increased delta Psf by 95% in WKY but to a lesser extent (by 26%) in SHR. In the same way, L-NNA decreased TP in MNS but not in MHS. The increase in delta Psf was 99% in MNS but only 32% in MHS. The EPFR reduction after TGF activation was significantly increased in WKY and MNS but relatively unchanged in SHR and MHS. The results show that the effect of intratubular NO synthase inhibition on TGF is impaired in both strains of hypertensive rats.

scholarly journals Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury

2021 ◽  
Vol 22 (3) ◽  
pp. 1382
Author(s):  
Jelena Nesovic Ostojic ◽  
Milan Ivanov ◽  
Nevena Mihailovic-Stanojevic ◽  
Danijela Karanovic ◽  
Sanjin Kovacevic ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protein Expression ◽  
Hyperbaric Oxygen ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate

2014 ◽  
Vol 163 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Shao-Ju Chien ◽  
Kuan-Miao Lin ◽  
Hsuan-Chang Kuo ◽  
Chien-Fu Huang ◽  
Ying-Jui Lin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Contribution of Vascular Nitric Oxide to Basal Blood Pressure in Conscious Spontaneously Hypertensive Rats and Normotensive Wistar Kyoto Rats

1995 ◽  
Vol 89 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Naoyoshi Minami ◽  
Yutaka Imai ◽  
Jun-Ichiro Hashimoto ◽  
Keishi Abe
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Methyl Ester ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Basal Blood Pressure ◽  
Wistar Kyoto

1. The aim of this study was to clarify the extent to which vascular nitric oxide contributes to basal blood pressure in conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. 2. The contribution of vascular nitric oxide to maintenance of blood pressure was estimated by measuring the pressor response to an intravenous injection of nitric oxide synthase inhibitor, Nω-l-arginine methyl ester, given after serial injections of captopril, vasopressin V1-receptor antagonist (V1-antagonist) and ganglion blocker (pentolinium) in conscious spontaneously hypertensive and Wistar Kyoto rats aged 20–28 weeks. To estimate the ‘amplifier property’ of hypertrophied vasculature in spontaneously hypertensive rats, which is known to modulate pressor responses, the lower blood pressure plateau after serial injections of captopril, V1-antagonist and pentolinium and the maximum blood pressure elicited by subsequent injection of increasing doses of phenylephrine were also measured. 3. The serial injections of captopril, V1-antagonist and pentolinium decreased mean arterial pressure from 164 ± 9 mmHg to 67 ± 2 mmHg and from 117 ± 2 mmHg to 49 ± 1 mmHg in spontaneously hypertensive and Wistar Kyoto rats respectively. The subsequent injection of Nω-l-arginine methyl ester restored mean arterial pressure almost to its control levels in both spontaneously hypertensive and Wistar Kyoto rats. The absolute changes in mean arterial pressure elicited by Nω-l-arginine methyl ester were significantly greater in spontaneously hypertensive than in Wistar Kyoto rats (P < 0.01), but there was no significant difference in the responses to Nω-l-arginine methyl ester when they were expressed as percentages of either the lower blood pressure plateau or maximum blood pressure. 4. These results indicate that basal blood pressure in both spontaneous hypertensive and Wistar Kyoto rats is maintained by a balance between vascular nitric oxide and major pressor systems. They also suggest that the vasodilatory effect of vascular nitric oxide does not differ between spontaneously hypertensive and Wistar Kyoto rats, and that the increased pressor effect of Nω-l-arginine methyl ester in spontaneously hypertensive rats is due to a vascular amplifier mechanism.

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