Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney

2004 ◽  
Vol 287 (1) ◽  
pp. R27-R32 ◽  
Author(s):  
Dewan S. A. Majid ◽  
Akira Nishiyama ◽  
Keith E. Jackson ◽  
Alexander Castillo
Keyword(s):  
Nitric Oxide ◽  
Protective Role ◽  
Potential Interaction ◽  
No Synthase ◽  
Anesthetized Dogs ◽  
Synthase Inhibitor ◽  
Qualitative Responses ◽  
Oxide Synthase ◽  
Renal Responses

To evaluate the role of a potential interaction between superoxide anion (O2−) and nitric oxide (NO) in regulating kidney function, we examined the renal responses to intra-arterial infusion of a superoxide dismutase mimetic, tempol (0.5 mg·kg−1·min−1), in anesthetized dogs treated with or without NO synthase inhibitor, Nω-nitro-l-arginine (NLA; 50 μg·kg−1·min−1). In one group of dogs ( n = 10), tempol infusion alone for 30 min before NLA infusion did not cause any significant changes in renal blood flow (RBF; 5.2 ± 0.4 to 5.0 ± 0.4 ml·min−1·g−1), glomerular filtration rate (GFR; 0.79 ± 0.04 to 0.77 ± 0.04 ml·min−1·g−1), urine flow (V; 13.6 ± 2.1 to 13.9 ± 2.5 μl·min−1·g−1), or sodium excretion (UNaV; 2.4 ± 0.3 to 2.2 ± 0.3 μmol·min−1·g−1). Interestingly, when tempol was infused in another group of dogs ( n = 12) pretreated with NLA, it caused increases in V (4.4 ± 0.4 to 9.7 ± 1.4 μl·min−1·g−1) and in UNaV (0.7 ± 0.1 to 1.3 ± 0.2 μmol·min−1·g−1) without affecting RBF or GFR. Although NO inhibition caused usual qualitative responses in both groups of dogs, the antidiuretic (47 ± 5 vs. 26 ± 4%) and antinatriuretic (67 ± 4 vs. 45 ± 11%) responses to NLA were seen much less in dogs pretreated with tempol. NLA infusion alone increased urinary excretion of 8-isoprostane (13.9 ± 2.7 to 22.8 ± 3.6 pg·min−1·g−1; n = 7), which returned to the control levels (11.6 ± 3.4 pg·min−1·g−1) during coadministration of tempol. These data suggest that NO synthase inhibition causes enhancement of endogenous O2− levels and support the hypothesis that NO plays a protective role against the actions of O2− in the kidney.

Superoxide scavenging attenuates renal responses to ANG II during nitric oxide synthase inhibition in anesthetized dogs

2005 ◽  
Vol 288 (2) ◽  
pp. F412-F419 ◽  
Author(s):  
Dewan S. A. Majid ◽  
Akira Nishiyama ◽  
Keith E. Jackson ◽  
Alexander Castillo
Keyword(s):  
Nitric Oxide ◽  
Urinary Sodium Excretion ◽  
Ang Ii ◽  
Arterial Infusion ◽  
Anesthetized Dogs ◽  
Significant Attenuation ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Renal Responses

To assess the role of superoxide (O2−) and nitric oxide (NO) interaction in mediating the renal actions of ANG II, we examined the renal responses to intra-arterial infusion of ANG II (0.5 ng·kg−1·min−1) before and during administration of a superoxide dismutase mimetic, tempol (0.5 mg·kg−1·min−1), in the presence or absence of NO synthase inhibitor, nitro-l-arginine (NLA; 50 μg·kg−1·min−1), in anesthetized dogs pretreated with enalaprilat (33 μg·kg−1·min−1). In one group of dogs ( n = 7), ANG II infusion before tempol infusion caused decreases of 24 ± 4% in renal blood flow (RBF), 55 ± 7% in urine flow (V), and 53 ± 8% in urinary sodium excretion (UNaV) with a slight decrease in glomerular filtration rate (GFR; −7.8 ± 3.4%). Tempol infusion alone did not cause significant alterations in RBF, GFR, V, or UNaV; however, ANG II in the presence of tempol caused a smaller degree of decreases in RBF (−12 ± 2%), in V (−16 ± 5%), and in UNaV (−27 ± 10%) with a slight increase in GFR (6.6 ± 2.8%) than the responses observed before tempol. In another group of NLA-treated dogs ( n = 6), tempol infusion also caused significant attenuation in the ANG II-induced responses on RBF (−13 ± 3% vs. −22 ± 7%), GFR (−19 ± 5% vs. −33 ± 3), V (−15 ± 12% vs. −28 ± 4%), and UNaV (−11 ± 14% vs. −32 ± 7%). These data demonstrate that renal responses to ANG II are partly mediated by O2− generation and its interaction with NO. The sodium-retaining effect of ANG II is greatly influenced by O2− generation, particularly in the condition of NO deficiency.

scholarly journals Involvement of tumor necrosis factor-α in natriuretic response to systemic infusion of nitric oxide synthase inhibitor in anesthetized mice

2010 ◽  
Vol 299 (1) ◽  
pp. F217-F224 ◽  
Author(s):  
Mohd Shahid ◽  
Joseph Francis ◽  
Khalid Matrougui ◽  
Dewan S. A. Majid
Keyword(s):  
Nitric Oxide ◽  
Kidney Tissue ◽  
No Synthase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Renal Vasoconstriction ◽  
Tnf Α ◽  
Synthase Inhibitor ◽  
Factor Α ◽  
Oxide Synthase ◽  
Renal Responses

Systemic infusion of TNF-α exerts renal vasoconstriction but caused marked natriuresis in mice. Similar renal responses were also observed during systemic infusion of nitric oxide (NO) synthase inhibitors as opposed to their usual antinatriuretic responses when administered intrarenally. In the present study, we examined the hypothesis that acute NO blockade systemically induces TNF-α generation. which induces this natriuretic response. Renal responses to intravenous infusion of the NO synthase inhibitor nitro-l-arginine methyl ester (l-NAME; 0.2 μg·min−1·g body wt−1 for 85 min) and its impact on the plasma level of TNF-α were evaluated in anesthetized mice. Plasma TNF-α was undetected in untreated mice ( n = 7) but was elevated in l-NAME-treated mice (109 ± 22 pg/ml; P < 0.01 vs. untreated group; n = 7) along with an increase in TNF-α protein expression in kidney tissue. l-NAME infusion caused a usual increase in mean arterial pressure (MAP; 98 ± 3 to 122 ± 3 mmHg; P < 0.01) and decreases in renal blood flow (RBF; 8.6 ± 0.3 to 4.4 ± 0.2 ml·min−1·g−1; P < 0.01) and glomerular filtration rate (GFR; 1.14 ± 0.07 to 0.77 ± 0.04 ml·min−1·g−1; P < 0.01) with a marked increase in sodium excretion (UNaV; 0.48 ± 0.10 to 3.52 ± 0.85 μmol·min−1·g−1; P < 0.01). Interestingly, in mice ( n = 7) pretreated with the TNF-α blocker etanercept (5 mg/kg sc), the UNaV response to l-NAME infusion was markedly blunted (0.58 ± 0.08 to 1.22 ± 0.28 μmol·min−1·g−1; P = NS) although responses for MAP, RBF, and GFR were mostly unchanged. However, pretreatment with the superoxide scavenger tempol in mice ( n = 7) did not alter the UNaV response to l-NAME. These data demonstrate that l-NAME-induced natriuresis is mediated, at least in part, by concomitant generation of TNF-α during NO blockade.

scholarly journals Blockade of neuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit

1998 ◽  
Vol 274 (1) ◽  
pp. R181-R186 ◽  
Author(s):  
Hiroshi Murakami ◽  
Jun-Li Liu ◽  
Hirohito Yoneyama ◽  
Yasuhiro Nishida ◽  
Kenji Okada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
No Synthase ◽  
Baroreflex Control ◽  
Neuronal No Synthase ◽  
Significant Difference ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Oxide Synthase

In previous studies we used N G-nitro-l-arginine (l-NNA) to investigate the role of nitric oxide (NO) in baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA).l-NNA increased resting mean arterial pressure (MAP), decreased HR, and did not change or slightly decreased RSNA. These changes complicated the assessment of the central effects of NO on the baroreflex control of HR and RSNA. Therefore, in the present study the effects of the relatively selective neuronal NO synthase inhibitor 7-nitroindazole (7-NI) on the baroreflex control of HR and RSNA were investigated in rabbits. Intraperitoneal injection of 7-NI (50 mg/kg) had no effect on resting HR, MAP, or RSNA. 7-NI significantly reduced the lower plateau of the HR-MAP baroreflex curve from 140 ± 4 to 125 ± 4 and from 177 ± 10 to 120 ± 9 beats/min in conscious and anesthetized preparations, respectively ( P < 0.05). In contrast, there was no significant difference in the RSNA-MAP curves before and after 7-NI administration in conscious or anesthetized preparations. These data suggest that blockade of neuronal NO synthase influences baroreflex control of HR but not of RSNA in rabbits.

Role of nitric oxide in adrenal catecholamine secretion in anesthetized dogs

1998 ◽  
Vol 275 (4) ◽  
pp. R1075-R1081 ◽  
Author(s):  
Takahiro Nagayama ◽  
Akio Hosokawa ◽  
Makoto Yoshida ◽  
Mizue Suzuki-Kusaba ◽  
Hiroaki Hisa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Splanchnic Nerve ◽  
Inhibitory Effect ◽  
No Synthase ◽  
Catecholamine Secretion ◽  
No Donor ◽  
Anesthetized Dogs ◽  
Synthase Inhibitor ◽  
Splanchnic Nerve Stimulation

We examined the role of nitric oxide (NO) in adrenal catecholamine secretion in response to splanchnic nerve stimulation (SNS) and exogenous acetylcholine (ACh) in anesthetized dogs. The NO synthase inhibitor N ω-nitro-l-arginine methyl ester (l-NAME), NO donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)- N-methyl-1-propanamine (NOC 7), and ACh were administered intra-arterially into the adrenal gland. The increases in catecholamine output induced by ACh (0.75–3 μg) were enhanced byl-NAME (0.1–1 mg/min) and inhibited by NOC 7 (0.2–2 μg/min). Inhibition by NOC 7 (2 μg/min) was observed during treatment withl-NAME (1 mg/min). The increases in catecholamine output induced by SNS (1–2 Hz) were inhibited byl-NAME and by NOC 7. No inhibitory effect of NOC 7 was observed during treatment withl-NAME. These results suggest that NO may play an inhibitory role in the regulation of adrenal catecholamine secretion in response to exogenous ACh.

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 Vasoactivity of adenosine in the trout (Oncorhynchus mykiss) coronary system: involvement of nitric oxide and interaction with noradrenaline

1998 ◽  
Vol 201 (22) ◽  
pp. 3075-3083 ◽  
Author(s):  
T Mustafa ◽  
C Agnisola
Keyword(s):  
Nitric Oxide ◽  
Constant Pressure ◽  
Constant Flow ◽  
Nitric Oxide Synthase Inhibitor ◽  
Heart Preparation ◽  
Synthase Inhibitor ◽  
Coronary Endothelium ◽  
Oxide Synthase ◽  
Working Heart

A vasoconstrictory response to adenosine has been reported in coronary rings from fish. Since the reactivity of the large coronary arteries and the microcirculation may differ, the present study was undertaken to determine the role of adenosine in the intact coronary system of trout under constant pressure or flow using an isolated and non-working heart preparation. The involvement of nitric oxide (NO) and the interaction with noradrenaline were also studied. At 10(-9) to 10(-8 )mol l-1, adenosine caused a vasoconstrictory response, whereas between 10(-7) and 10(-5 )mol l-1 the response was predominantly vasodilative. Theophylline abolished both these responses to adenosine. The vasodilation induced by adenosine (at 10(-5 )mol l-1) was significantly reduced when the preparation was perfused under constant-flow than rather under constant-pressure conditions. The nitric oxide synthase inhibitor N-nitro-l-arginine (l-NA, 10(-4 )mol l-1) partially reduced the vasodilation induced by adenosine (at 10(-5 )mol l-1) under constant-pressure but not under constant-flow conditions. Perfusion of the intact coronary system with l-arginine or with adenosine significantly increased the rate of nitrite (NO2-) release, while perfusion with l-NA or theophylline reduced NO2- release. Chemical denudation of the coronary endothelium by CHAPS resulted in the loss of both the l-arginine- and adenosine-mediated vasodilation and the l-arginine-induced increase in the rate of NO2- release. Adenosine (10(-5 )mol l-1) offset and overrode the vasoconstriction induced by 10(-7 )mol l-1 noradrenaline. l-NA inhibited only the adenosine-induced vasodilation but not the ability to offset noradrenaline vasoconstriction, excluding the involvement of NO in the interaction between adenosine and noradrenaline.

Nitric oxide as a regulator of adrenal blood flow

1993 ◽  
Vol 264 (2) ◽  
pp. H464-H469 ◽  
Author(s):  
M. J. Breslow ◽  
J. R. Tobin ◽  
D. S. Bredt ◽  
C. D. Ferris ◽  
S. H. Snyder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Neural Control ◽  
Splanchnic Nerve ◽  
No Synthase ◽  
Catecholamine Secretion ◽  
Before And After ◽  
Anesthetized Dogs ◽  
Synthase Inhibitor ◽  
Splanchnic Nerve Stimulation

To determine whether nitric oxide (NO) is involved in adrenal medullary vasodilation during splanchnic nerve stimulation (NS)-induced catecholamine secretion, blood flow (Q) and secretory responses were measured in pentobarbital-anesthetized dogs before and after administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). L-NAME (40 mg/kg iv over 5 min, followed by 40 mg.kg-1.h-1) reduced NO synthase activity of medullary and cortical homogenates from 5.2 +/- 0.3 to 0.7 +/- 0.1 pmol.min-1.mg protein-1 and from 1.2 +/- 0.2 pmol.min-1.mg protein-1 to undetectable levels, respectively. L-NAME reduced resting medullary and cortical Q by 42 and 60%, respectively. NS before L-NAME increased medullary Q from 181 +/- 16 to 937 +/- 159 ml.min-1.100 g-1 and epinephrine secretion from 1.9 +/- 0.8 to 781 +/- 331 ng/min. NS after L-NAME had no effect on medullary Q (103 +/- 14 vs. 188 +/- 34 ml.min-1.100 g-1), while epinephrine secretion increased to the same extent as in control animals (1.9 +/- 0.7 vs. 576 +/- 250 ng/min). L-NAME also unmasked NS-induced cortical vasoconstriction; cortical Q decreased from 96 +/- 8 to 50 +/- 5 ml.min-1.100 g-1. Administration of hexamethonium (30 mg/kg iv), a nicotinic receptor antagonist, reduced NS-induced epinephrine secretion by 90%. These data suggest independent neural control of medullary Q and catecholamine secretion, the former by NO and the latter by acetylcholine.

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.

Effects of nitric oxide synthase inhibition on cutaneous vasodilation during body heating in humans

1998 ◽  
Vol 85 (3) ◽  
pp. 830-834 ◽  
Author(s):  
Shubha Shastry ◽  
Niki M. Dietz ◽  
John R. Halliwill ◽  
Ann S. Reed ◽  
Michael J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Potential Role ◽  
Contralateral Side ◽  
Laser Doppler ◽  
Cutaneous Vasodilation ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Cutaneous Vascular Conductance ◽  
Cutaneous Blood

We sought to examine further the potential role of nitric oxide (NO) in the neurally mediated cutaneous vasodilation in nonacral skin during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured by using laser-Doppler flowmeters placed on both forearms. The NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA) was given selectively to one forearm via a brachial artery catheter after marked cutaneous vasodilation had been established. During body heating, oral temperature increased by 1.1 ± 0.1°C while heart rate increased by 30 ± 6 beats/min. Mean arterial pressure stayed constant at 84 ± 2 mmHg. In the experimental forearm, cutaneous vascular conductance (CVC; laser-Doppler) decreased to 86 ± 5% of the peak response to heating ( P < 0.05 vs. pre-l-NMMA values) afterl-NMMA infusion. In some subjects, l-NMMA caused CVC to fall by ∼30%; in others, it had little impact on the cutaneous circulation. CVC in the control arm showed a similar increase with heating, then stayed constant whilel-NMMA was given to the contralateral side. These results demonstrate that NO contributes modestly, but not consistently, to cutaneous vasodilation during body heating in humans. They also indicate that NO is not the only factor responsible for the dilation.

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