Hemodynamic and renal effects of acute and progressive nitric oxide synthesis inhibition in anesthetized dogs

2001 ◽  
Vol 280 (1) ◽  
pp. R143-R148 ◽  
Author(s):  
Aleix Cases ◽  
John Haas ◽  
John C. Burnett ◽  
Juan Carlos Romero
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Methyl Ester ◽  
Ester Group ◽  
Pulmonary Vasculature ◽  
Control Group ◽  
No Production ◽  
Dependent Manner ◽  
Synthesis Inhibition ◽  
Anesthetized Dogs

This study evaluated the effects of progressive nitric oxide (NO) inhibition in the regulation of systemic and regional hemodynamics and renal function in anesthetized dogs. The N G-nitro-l-arginine methyl ester group ( n = 9) received progressive doses of 0.1, 1, 10, and 50 μg · kg−1 · min−1. Renal (RBF), mesenteric (MBF), iliac (IBF) blood flows, mean arterial pressure (MAP), pulmonary pressures, cardiac output (CO), and systemic and pulmonary vascular resistances were measured. During N G-nitro-l-arginine methyl ester infusion, MAP and systemic vascular resistances increased in a dose-dependent manner. Mean pulmonary pressure and pulmonary vascular resistances increased in both the N G-nitro-l-arginine methyl ester and the control group, but the increase was more marked in the N G-nitro-l-arginine methyl ester group during the last two infusion periods. CO decreased progressively, before any significant change in blood pressure was noticeable in the N G-nitro-l-arginine methyl ester group. IBF decreased significantly from the first N G-nitro-l-arginine methyl ester dose, whereas RBF and MBF only decreased significantly during the highest N G-nitro-l-arginine methyl ester dose. Urinary volume and sodium excretion only increased significantly in the time control group during the two last time periods. The pulmonary vasculature was more sensitive than the systemic vasculature, whereas skeletal muscle and renal vasculatures showed a greater sensitivity to the inhibition of NO production than the mesenteric vasculature. NO synthesis inhibition induces a progressive antidiuretic and antinatriuretic effect, which is partially offset by the increase in blood pressure.

Renal and pressor effects of aminoguanidine in cirrhotic rats with ascites.

1996 ◽  
Vol 7 (12) ◽  
pp. 2694-2699
Author(s):  
M C Ortíz ◽  
L A Fortepiani ◽  
C Martínez ◽  
N M Atucha ◽  
J García-Estañ
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Liver Cirrhosis ◽  
Experimental Model ◽  
Systemic Blood Pressure ◽  
Arterial Hypotension ◽  
Control Group ◽  
No Production ◽  
Water Excretion ◽  
Excretory Function

Recent work indicates that nitric oxide (NO) plays an important role in the systemic and renal alterations of liver cirrhosis. This study used aminoguanidine (AG), a preferential inhibitor of inducible nitric oxide synthase (iNOS), to evaluate the role of this NOS isoform in the systemic and renal alterations of an experimental model of liver cirrhosis with ascites (carbon tetrachloride/ phenobarbital). Experiments have been performed in anesthetized cirrhotic rats and their respective control rats prepared for clearance studies. Administration of AG (10 to 100 mg/kg, iv) elevated dose-dependent mean arterial pressure (MAP, in mm Hg) in the cirrhotic rats from a basal level of 79.3 +/- 3.6 to 115.0 +/- 4.7, whereas in the control animals, MAP increased only with the highest dose of the inhibitor (from 121.8 +/- 3.6 to 133.3 +/- 1.4). In the cirrhotic group, AG also significantly increased sodium and water excretion, whereas these effects were very modest in the control group. Plasma concentration of nitrates+nitrites, measured as an index of NO production, were significantly increased in the cirrhotic animals in the basal period and decreased with AG to levels not significantly different from the control animals. Similar experiments performed with the nonspecific NOS inhibitor N omega-nitro-L-arginine (NNA) also demonstrated an increased pressor sensitivity of the cirrhotic rats, but the arterial hypotension was completely corrected. These results, in an experimental model of liver cirrhosis with ascites, show that AG exerts a beneficial effect as a result of inhibition of NO production, increasing blood pressure and improving the reduced excretory function. Because NNA, but not AG, completely normalized the arterial hypotension, it is suggested that the constitutive NOS isoform is also contributing in an important degree. It is concluded that the activation of both inducible and constitutive NOS isoforms plays an important role in the lower systemic blood pressure and associated abnormalities that characterize liver cirrhosis.

Systemic inhibition of nitric oxide and prostaglandins in volume-induced natriuresis and hypertension

1998 ◽  
Vol 274 (1) ◽  
pp. R175-R180 ◽  
Author(s):  
James D. Krier ◽  
Juan Carlos Romero
Keyword(s):  
Nitric Oxide ◽  
Mean Arterial Pressure ◽  
Methyl Ester ◽  
Arterial Pressure ◽  
Volume Expansion ◽  
Isotonic Saline ◽  
Significant Elevation ◽  
Synthesis Inhibition ◽  
Anesthetized Dogs ◽  
Change Map

Nitric oxide (NO) synthesis inhibition with N G-nitro-l-arginine methyl ester (l-NAME) (10 μg ⋅ kg−1 ⋅ min−1iv), cyclooxygenase inhibition with meclofenamate (Meclo; 5 mg/kg iv bolus), and combination of drugs (l-NAME+Meclo) were used to investigate the roles of NO and prostaglandins (PG) in the hemodynamic and natriuretic responses to isotonic saline volume expansion (VE; 5% body wt over 60 min) in anesthetized dogs. Before VE,l-NAME ( n = 6), Meclo ( n = 6), andl-NAME+Meclo ( n = 6) produced significant increments in mean arterial pressure (MAP) of 12 ± 2, 15 ± 3, and 17 ± 3 mmHg, respectively. VE did not change MAP in Meclo-treated dogs, but produced a significant elevation in the control dogs (14 ± 6 mmHg), inl-NAME-treated dogs (17 ± 6 mmHg), and in dogs pretreated withl-NAME+Meclo (12 ± 5 mmHg). VE alone induced marked natriuretic responses in the control (38 ± 9 to 562 ± 86 μmol/min),l-NAME (31 ± 9 to 664 ± 65 μmol/min), and Meclo groups (41 ± 10 to 699 ± 51 μmol/min). However, this natriuretic response was attenuated in dogs pretreated with l-NAME+Meclo (12 ± 4 to 185 ± 52 μmol/min). These results indicate that 1) blockade of both NO and PGs has significant diminishing effects on volume-induced natriuresis, 2) NO blockade alone impairs volume-induced natriuresis in a manner that requires further increases in MAP to restore the natriuresis, and 3) PG blockade alone does not curtail volume-induced natriuresis.

scholarly journals Factors Regulating Nitric Oxide Production in Spontaneously Hypertensive Rats Treated with Piper Sarmentosum Aqueous Extract

2020 ◽  
Vol 18 (3) ◽  
Author(s):  
Mohd Zainudin M ◽  
Elshami TFT ◽  
Ismawi HR ◽  
Hashim Fauzy F ◽  
Abdul Razak T
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Aqueous Extract ◽  
Antioxidant Activities ◽  
Control Group ◽  
No Production ◽  
Hypertensive Rats ◽  
Reducing Ability ◽  
Freeze Dried

Introduction: Hypertension is a major risk factor for cardiovascular diseases which is one of the leading causes of death worldwide. Piper sarmentosum (PS) has been widely used in traditional medicine with proven antihypertensive and antioxidant effects. This study aims to evaluate the antihypertensive potential of PS aqueous extract (PSAE) and to investigate the factors modulating nitric oxide (NO) production through its anti-oxidant activities. Methods: PS leaves were extracted with distilled water, freeze-dried and examined to quantify their antioxidant activities through 2,2-diphenyl-1-picrylhydrazyl and ferric reducing ability plasma test. The antihypertensive effect of PSAE in spontaneous hypertensive rats (SHR) was evaluated using four different groups (n=6); C (negative control), K (PSAE 500mg/kg), P (3 mg/kg perindopril) and M (PSAE 500 mg/kg + 1.5 mg/kg perindopril). PSAE and other treatments were given via oral gavage for 28 days. The blood pressure (BP) was determined using the non-invasive BP monitoring tail cuff technique and recorded weekly. SHR’s blood was collected to determine the serum NO level using Griess assay. Asymmetric dimethylarginine (ADMA) and arginine levels were determined using high performance liquid chromatography. Results: The extract showed good in-vitro antioxidant activities and a significant reduction in both systolic and diastolic BP compared to control group. They were also a decrease in plasma ADMA and an increase in serum NO level. Meanwhile, arginine level does not change significantly. Conclusion: High in-vitro antioxidant activities in PSAE enhances the clearance of ADMA that leads to an increase in serum NO production hence ameliorating the blood pressure of SHR.

Hypoxia, alpha 2-adrenergic, and nitric oxide-dependent interactions on canine cerebral blood flow

1994 ◽  
Vol 266 (2) ◽  
pp. H476-H482 ◽  
Author(s):  
R. W. McPherson ◽  
R. C. Koehler ◽  
R. J. Traystman
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Methyl Ester ◽  
No Synthase ◽  
Hypoxic Hypoxia ◽  
Control Group ◽  
O2 Transport ◽  
Anesthetized Dogs

We tested the hypothesis that NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) and alpha 2-adrenoreceptor stimulation with dexmedetomidine (Dex) decreases the cerebral blood flow (CBF) response to hypoxia. In isoflurane-anesthetized dogs, CBF was measured during two episodes of hypoxic hypoxia. In a control group (n = 6), CBF increased similarly from 83 +/- 4 to 210 +/- 30 ml.min-1 x 100 g-1 and from 88 +/- 7 to 205 +/- 27 (+/- SE) ml.min-1 x 100 g-1 during two hypoxic episodes. In a second group (n = 6), hypoxia increased CBF from 88 +/- 15 to 204 +/- 38 ml.min-1 x 100 g-1. Dex (10 micrograms/kg i.v.) reduced normoxic CBF to 54 +/- 8 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 97 +/- 14 ml.min-1 x 100 g-1. In a third group pretreated with L-NAME (40 mg/kg i.v.) 1 h before anesthesia (n = 6), normoxic CBF was less than in the control group (52 +/- 2 vs. 83 +/- 4 ml.min-1 x 100 g-1). Hypoxia increased CBF to 177 +/- 13 ml.min-1 x 100 g-1. Dex after L-NAME further decreased normoxic CBF to 37 +/- 3 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 106 +/- 18 ml.min-1 x 100 g-1. Dex, L-NAME, and Dex + L-NAME each reduced cerebral O2 transport (CBF x arterial O2 content) during normoxia, but the increase in CBF during hypoxia was sufficient to prevent further decreases in O2 transport. Thus the response to hypoxia remained proportional to normoxic levels of CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Myocardial Injury ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Oxide Synthase ◽  
Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure

1991 ◽  
Vol 261 (6) ◽  
pp. F1033-F1037 ◽  
Author(s):  
V. Lahera ◽  
M. G. Salom ◽  
F. Miranda-Guardiola ◽  
S. Moncada ◽  
J. C. Romero
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Function ◽  
Methyl Ester ◽  
Renal Plasma Flow ◽  
Urinary Sodium Excretion ◽  
Systemic Blood Pressure ◽  
Synthesis Inhibitor ◽  
Renal Changes ◽  
Dose Dependent

The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.

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.

Inhibition of nitric oxide synthesis attenuates pressure-induced natriuretic responses in anesthetized dogs

1993 ◽  
Vol 264 (1) ◽  
pp. F79-F87 ◽  
Author(s):  
D. S. Majid ◽  
A. Williams ◽  
L. G. Navar
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sodium Excretion ◽  
Renin Angiotensin System ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Synthesis Inhibition ◽  
Fractional Excretion Of Sodium ◽  
Anesthetized Dogs ◽  
Pressure Natriuresis

Inhibition of nitric oxide (NO) synthesis by intrarenal administration of nitro-L-arginine (NLA) leads to decreases in urinary sodium excretion (UNaV) in association with the increases in renal vascular resistance (RVR). In the present study, we examined the ability of the kidney to alter its sodium excretion in response to acute changes in renal arterial pressure (RAP) in anesthetized dogs before and during intrarenal infusion of NLA (50 micrograms.kg-1.min-1). NO synthesis inhibition in 11 dogs increased RVR by 32 +/- 4% and decreased renal blood flow (RBF) by 25 +/- 3%, outer cortical blood flow by 25 +/- 6%, urine flow by 37 +/- 14%, UNaV by 71 +/- 5%, and fractional excretion of sodium (FENa) by 71 +/- 4%. Glomerular filtration rate was not significantly changed during NLA infusion. As previously reported, there was suppression of the RBF autoregulation plateau during NO synthesis inhibition. In addition, there was a marked attenuation of urine flow and UNaV responses to reductions in RAP (150 to 75 mmHg), with significant reductions in the slopes of the relationships between RAP vs. UNaV and RAP vs. FENa during NLA infusion. Similar responses were observed in nine other dogs treated with the angiotensin receptor antagonist losartan, indicating that an augmented activity of the renin-angiotensin system is not responsible for attenuation of the slope of the pressure-natriuresis relationship during NLA infusion. These data suggest that NO may participate in the mediation of the pressure-natriuresis response.

Nitric oxide and cerebral blood flow responses to hyperbaric oxygen

2000 ◽  
Vol 88 (4) ◽  
pp. 1381-1389 ◽  
Author(s):  
Ivan T. Demchenko ◽  
Albert E. Boso ◽  
Thomas J. O'Neill ◽  
Peter B. Bennett ◽  
Claude A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Methyl Ester ◽  
No Production ◽  
No Donors ◽  
Mk 801 ◽  
Neuronal Excitation ◽  
Synthase Inhibitor ◽  
Electroencephalogram Eeg

We have tested the hypothesis that cerebral nitric oxide (NO) production is involved in hyperbaric O2 (HBO2) neurotoxicity. Regional cerebral blood flow (rCBF) and electroencephalogram (EEG) were measured in anesthetized rats during O2 exposure to 1, 3, 4, and 5 ATA with or without administration of the NO synthase inhibitor ( N ω-nitro-l-arginine methyl ester), l-arginine, NO donors, or the N-methyl-d-aspartate receptor inhibitor MK-801. After 30 min of O2 exposure at 3 and 4 ATA, rCBF decreased by 26–39% and by 37–43%, respectively, and was sustained for 75 min. At 5 ATA, rCBF decreased over 30 min in the substantia nigra by one-third but, thereafter, gradually returned to preexposure levels, preceding the onset of EEG spiking activity. Rats pretreated with N ω-nitro-l-arginine methyl ester and exposed to HBO2 at 5 ATA maintained a low rCBF. MK-801 did not alter the cerebrovascular responses to HBO2at 5 ATA but prevented the EEG spikes. NO donors increased rCBF in control rats but were ineffective during HBO2 exposures. The data provide evidence that relative lack of NO activity contributes to decreased rCBF under HBO2, but, as exposure time is prolonged, NO production increases and augments rCBF in anticipation of neuronal excitation.

scholarly journals Contribution of captopril thiol group to the prevention of spontaneous hypertension

2007 ◽  
pp. S41-S48
Author(s):  
O Pecháňová
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Ace Inhibitors ◽  
Thiol Group ◽  
No Synthase ◽  
Spontaneous Hypertension ◽  
Cgmp Level ◽  
Control Group ◽  
No Production ◽  
Enalapril Group

We aimed to compare the effect of angiotensin converting enzyme (ACE) inhibitors captopril (containing thiol group) and enalapril (without thiol group) on the development of spontaneous hypertension and to analyze mechanisms of their actions, particularly effects on oxidative stress and NO production. Six-week-old SHR were divided into three groups: control, group receiving captopril (50 mg/kg/day) or enalapril (50 mg/kg/day) for 6 weeks. At the end of experiment, systolic blood pressure (SBP) increased by 41 % in controls. Both captopril and enalapril prevented blood pressure increase, however, SBP in the captopril group (121+/-5 mmHg) was significantly lower than that in the enalapril group (140+/-5 mmHg). Concentration of conjugated dienes in the aorta was significantly lower in the captopril group compared to the enalapril group. Captopril and enalapril increased NO synthase activity in the heart and aorta to the similar level. Neither captopril nor enalapril was, however, able to increase the expression of eNOS. Both ACE inhibitors increased the level of cGMP. However, cGMP level was significantly higher in the aorta of captopril group. We conclude that captopril, beside inhibition of ACE, prevented hypertension by increasing NO synthase activity and by simultaneous decrease of oxidative stress which resulted in increase of cGMP concentration.

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