Downregulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH

1998 ◽  
Vol 274 (4) ◽  
pp. F642-F649 ◽  
Author(s):  
N. D. Vaziri ◽  
Z. Ni ◽  
X. Q. Wang ◽  
F. Oveisi ◽  
X. J. Zhou
Keyword(s):  
Nitric Oxide ◽  
Calcium Channel ◽  
Left Kidney ◽  
No Synthase ◽  
Channel Blockade ◽  
Calcium Channel Blockade ◽  
No Donor ◽  
Oxide Synthase ◽  
Hypotensive Response

The available data on the effect of chronic renal failure (CRF) on nitric oxide (NO) metabolism are limited and contradictory. We studied rats with CRF 6 wk after a five-sixths nephrectomy and compared the results with those in the sham-operated controls, felodipine-treated CRF, and parathyroidectomized (CRF-PTX) animals. CRF was produced by surgical resection of the upper and lower thirds of the left kidney, followed by contralateral nephrectomy. We chose this model, as opposed to that produced by renal artery branch ligation, because the latter causes exuberant hypertension (HTN), which independently affects NO metabolism. The CRF group exhibited a mild HTN coupled with elevated basal platelet cytosolic Ca2+concentration ([Ca2+]i), blunted hypotensive response tol-arginine, decreased hypertensive response to NO synthase (NOS) inhibitor, N G-monomethyl-l-arginine, and normal hypotensive response to NO donor, sodium nitroprusside. This was associated with a significant reduction in urinary excretion of stable NO metabolites (NOX) and depressed NOS activity, as well as endothelial and inducible NO synthase (eNOS and iNOS, respectively) protein contents of thoracic aorta and the remnant kidney in the CRF animals. Calcium channel blockade and PTX lowered blood pressure, increased urinary NOX, and enhanced vascular NOS activity, as well as eNOS and iNOS protein expressions in the tested tissues. Thus CRF animals exhibited significant reductions in vascular NOS activity and eNOS and iNOS expressions. These abnormalities were reversed by calcium channel blockade and PTX, suggesting the possible causal role of CRF-induced dysregulation of [Ca2+]i.

Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. R84-R88 ◽  
Author(s):  
M. Huang ◽  
M. L. Leblanc ◽  
R. L. Hester
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
No Synthase ◽  
Before And After ◽  
Regional Hemodynamics ◽  
Autonomic Blockade ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.

scholarly journals Nitric oxide-induced cardioprotection in cultured rat ventricular myocytes

2000 ◽  
Vol 278 (4) ◽  
pp. H1211-H1217 ◽  
Author(s):  
Roby D. Rakhit ◽  
Richard J. Edwards ◽  
James W. Mockridge ◽  
Anwar R. Baydoun ◽  
Amanda W. Wyatt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ventricular Myocytes ◽  
Culture Conditions ◽  
Neonatal Rat ◽  
No Donor ◽  
Rat Ventricular Myocytes ◽  
Kinase C ◽  
Neonatal Rat Ventricular Myocytes ◽  
Oxide Synthase

The aim of this study was to investigate the role of nitric oxide (NO) in a cellular model of early preconditioning (PC) in cultured neonatal rat ventricular myocytes. Cardiomyocytes “preconditioned” with 90 min of stimulated ischemia (SI) followed by 30 min reoxygenation in normal culture conditions were protected against subsequent 6 h of SI. PC was blocked by N G-monomethyl-l-arginine monoacetate but not by dexamethasone pretreatment. Inducible nitric oxide synthase (NOS) protein expression was not detected during PC ischemia. Pretreatment (90 min) with the NO donor S-nitroso- N-acetyl-l,l-penicillamine (SNAP) mimicked PC, resulting in significant protection. SNAP-triggered protection was completely abolished by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) but was unaffected by chelerythrine or the presence of glibenclamide and 5-hydroxydecanoate. With the use of RIA, SNAP treatment increased cGMP levels, which were blocked by ODQ. Hence, NO is implicated as a trigger in this model of early PC via activation of a constitutive NOS isoform. After exposure to SNAP, the mechanism of cardioprotection is cGMP dependent but independent of protein kinase C or ATP-sensitive K+ channels. This differs from the proposed mechanism of NO-induced cardioprotection in late PC.

Is nitric oxide the final mediator regulating the migrating myoelectric complex cycle?

1995 ◽  
Vol 268 (2) ◽  
pp. G207-G214 ◽  
Author(s):  
A. Rodriguez-Membrilla ◽  
V. Martinez ◽  
M. Jimenez ◽  
E. Gonalons ◽  
P. Vergara
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
Motor Pattern ◽  
No Synthase ◽  
Phase Iii ◽  
Motor Patterns ◽  
No Donor ◽  
Postprandial State ◽  
Synthase Inhibitor

The main objective was to study the role of nitric oxide (NO) in the conversion of migrating myoelectric complexes (MMC) to the irregular electrical activity characteristic of the postprandial state. Both rats and chickens were implanted with electrodes for electromyography in the small intestine. Intravenous infusion of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, induced an organized MMC-like pattern in fed rats. Infusion of sodium nitroprusside, a NO donor, disrupted the MMC, inducing a postprandial-like motor pattern in fasting rats. Similarly, in chickens L-NNA mimicked the fasting pattern, consisting of a shortening of phase II, enlargement of phase III, orad displacement of the origin of the MMC, and an increase in the speed of phase III propagation. An inhibition of NO synthesis seems to be involved in the induction of the fasting motor pattern, whereas an increase of NO mediates the occurrence of the fed pattern. It is suggested that NO might be the final mediator in the control of small intestine motor patterns.

scholarly journals Nitric oxide synthase acutely regulates progesterone production by in vitro cultured rabbit corpora lutea

1999 ◽  
Vol 160 (2) ◽  
pp. 275-283 ◽  
Author(s):  
A Gobbetti ◽  
C Boiti ◽  
C Canali ◽  
M Zerani
Keyword(s):  
Nitric Oxide ◽  
In Vitro Release ◽  
Inhibitory Effect ◽  
Corpora Lutea ◽  
No Donor ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Vitro Release

We examined the presence and the regulation of nitric oxide (NO) synthase (NOS) using in vitro cultured corpora lutea (CL) obtained from rabbits at days 4 and 9 of pseudopregnancy. The role of NO and NOS on steroidogenesis was also investigated using the same CL preparations after short-term incubations (30 min and 2 h) with the NO donor, sodium nitroprusside (NP), the NOS inhibitor, Nomega-nitro-l-arginine methyl ester (l-NAME) and prostaglandin (PG) F-2alpha. The basal NOS activity was greater in CL at day 4 than at day 9, and was also differently modulated by PGF-2alpha, depending on the age of the CL. The addition of PGF-2alpha to day 4 CL had no effect, but PGF-2alpha on day 9 caused a threefold increase in NOS activity. NP caused a two- to fivefold decrease in release of progesterone from CL of both ages, and this inhibitory effect on steroidogenesis was reversed by l-NAME. All treatments failed to modify basal androgens and 17beta-oestradiol was not detectable in either control or treated CL. These results suggest that NO is effectively involved in the regulation process of steroidogenesis, independently of 17beta-oestradiol. PGF-2alpha had no effect on day 4, but induced luteolysis on day 9, by reducing progesterone (P</=0. 01) to about 18% of control. The luteolytic action of PGF-2alpha was completely reversed by co-incubation with l-NAME, thus supporting the hypothesis that luteolysis is mediated by NO. The addition of NP or l-NAME did not modify the in vitro release of PGF-2alpha. We hypothesised that PGF-2alpha upregulates NOS activity and, consequently, the production of NO, which acutely inhibits progesterone release from day 9 CL of pseudopregnant rabbits.

Effect of chronic lithium administration on endothelium-dependent relaxation of rat mesenteric bed: role of nitric oxide

2007 ◽  
Vol 85 (10) ◽  
pp. 1038-1046 ◽  
Author(s):  
Banafsheh Afsharimani ◽  
Leila Moezi ◽  
Hamed Sadeghipour ◽  
Bahareh Rahimzadeh-Rofouyi ◽  
Maliheh Nobakht ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nadph Diaphorase ◽  
Control Group ◽  
No Donor ◽  
Vascular Bed ◽  
Mesenteric Vascular Bed ◽  
Vascular Beds ◽  
Oxide Synthase ◽  
And Control

The mechanism of action of lithium, an effective treatment for bipolar disease, is still unknown. In this study, the mesenteric vascular beds of control rats and rats that were chronically treated with lithium were prepared by the McGregor method, and the mesenteric vascular bed vasorelaxation responses were examined. NADPH-diaphorase histochemistry was used to determine the activity of NOS (nitric oxide synthase) in mesenteric vascular beds. We demonstrated that ACh-induced vasorelaxation increased in the mesenteric vascular bed of rats treated with lithium. Acute Nο-nitro-l-arginine methyl ester (l-NAME) administration in the medium blocked ACh-induced vasorelaxation in the control group more effectively than in lithium-treated rats, while the vasorelaxant response to sodium nitroprusside, a NO donor, was not different between lithium-treated and control groups. Acute aminoguanidine administration blocked ACh-induced vasorelaxation of lithium-treated rats, but had no effect in the control rats. Furthermore, NOS activity, determined by NADPH-diaphorase staining, was significantly greater in the mesenteric vascular beds from chronic lithium-treated rats than in those from control rats. These data suggest that the enhanced ACh-induced endothelium-derived vasorelaxation in rat mesenteric bed from chronic lithium-treated rats might be associated with increased NOS activity, likely via iNOS. Simultaneous acute l-NAME and indomethacin administration suggests the possible upregulation of EDHF (endothelium-derived hyperpolarizing factor) in lithium-treated rats.

Evidence that nitric oxide increases glucose transport in skeletal muscle

1997 ◽  
Vol 82 (1) ◽  
pp. 359-363 ◽  
Author(s):  
Thomas W. Balon ◽  
Jerry L. Nadler ◽  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Glucose Transport ◽  
Type I ◽  
Stimulation Protocol ◽  
No Donor ◽  
Nos Inhibitor ◽  
Exercise Induced ◽  
Oxide Synthase

Balon, Thomas W., and Jerry L. Nadler. Evidence that nitric oxide increases glucose transport in skeletal muscle. J. Appl. Physiol. 82(1): 359–363, 1997.—Nitric oxide synthase (NOS) is expressed in skeletal muscle. However, the role of nitric oxide (NO) in glucose transport in this tissue remains unclear. To determine the role of NO in modulating glucose transport, 2-deoxyglucose (2-DG) transport was measured in rat extensor digitorum longus (EDL) muscles that were exposed to either a maximally stimulating concentration of insulin or to an electrical stimulation protocol, in the presence of N G-monomethyl-l-arginine, a NOS inhibitor. In addition, EDL preparations were exposed to sodium nitroprusside (SNP), an NO donor, in the presence of submaximal and maximally stimulating concentrations of insulin. NOS inhibition reduced both basal and exercise-enhanced 2-DG transport but had no effect on insulin-stimulated 2-DG transport. Furthermore, SNP increased 2-DG transport in a dose-responsive manner. The effects of SNP and insulin on 2-DG transport were additive when insulin was present in physiological but not in pharmacological concentrations. Chronic treadmill training increased protein expression of both type I and type III NOS in soleus muscle homogenates. Our results suggest that NO may be a potential mediator of exercise-induced glucose transport.

Effect of nitric oxide on renin secretion. II. Studies in the perfused juxtaglomerular apparatus

1995 ◽  
Vol 268 (5) ◽  
pp. F953-F959 ◽  
Author(s):  
X. R. He ◽  
S. G. Greenberg ◽  
J. P. Briggs ◽  
J. B. Schnermann
Keyword(s):  
Nitric Oxide ◽  
Concentration Ratio ◽  
Juxtaglomerular Apparatus ◽  
No Synthase ◽  
Renin Secretion ◽  
Progressive Decrease ◽  
No Donor ◽  
Concentration Step ◽  
Synthase Inhibitor

To examine the possible role of NO in macula densa control of renin secretion, we examined the effects of varying NO availability on renin release in the isolated perfused rabbit juxtaglomerular apparatus (JGA). Gradual increments of luminal Na/Cl concentration ratio (mM/mM) from 26/7 over 46/27, 66/47, to 86/67 caused a progressive decrease in renin secretion from (as log of nano-Goldblatt hog units vs. time, i.e., log nGU/min) 1.09 +/- 0.34 to 0.46 +/- 0.24 log nGU/min, with the greatest change occurring at the first concentration step. The presence of 0.7 mM N omega-nitro-L-arginine (NNA), an NO synthase inhibitor, in the luminal fluid significantly reduced renin secretion at the lowest Na/Cl concentration ratio to 0.65 +/- 0.32 log nGU/min (P < 0.01 compared with control). Renin secretion at the higher Na/Cl concentration ratios was not significantly affected by NNA compared with control. In contrast to these results, the addition of the NO donor nitroprusside (1 mM) to the bath caused a reduction in renin secretion from 1.0 +/- 0.39 to 0.47 +/- 0.46 log nGU/min (P < 0.05), an effect that was reversed by bath addition of 0.01 mM methylene blue. Similarly, addition of L-arginine (0.7 mM) to the bath reduced renin secretion from 0.99 +/- 0.37 to 0.81 +/- 0.38 log nGU/min (P < 0.01), whereas addition of L-arginine to the luminal fluid increased renin secretion from 0.85 +/- 0.43 to 1.94 +/- 0.46 log nGU/min (P < 0.05). The stimulatory effect of luminal L-arginine was reversed by the luminal addition of NNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document