Inhibition of Endogenous Nitric Oxide Synthesis Potentiates the Effects of Sodium Nitroprusside but Not of Adenosine in Experimental Pulmonary Hypertension

Pharmacology ◽  
1999 ◽  
Vol 58 (1) ◽  
pp. 34-43 ◽  
Author(s):  
Michael H. Wall ◽  
Kenneth W. Patterson ◽  
Brian P. Kavanagh ◽  
RonaldG. Pearl
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Sodium Nitroprusside ◽  
Nitric Oxide Synthesis ◽  
Endogenous Nitric Oxide

Inhibition of Endogenous Nitric Oxide Synthase Potentiates Nitrovasodilators in Experimental Pulmonary Hypertension

1996 ◽  
Vol 85 (4) ◽  
pp. 860-866 ◽  
Author(s):  
Brian P. Kavanagh ◽  
John S. Thompson ◽  
Ronald G. Pearl
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Sodium Nitroprusside ◽  
Dose Response ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
No Synthase ◽  
Pulmonary Vasculature ◽  
Response Characteristics ◽  
Endogenous Nitric Oxide

Background The role of endogenous nitric oxide (NO) in the regulation of pulmonary vascular tone is complex. Inhibition of endogenous NO synthase, potentially through upregulation of guanylyl cyclase, results in an increase in potency of nitrovasodilators in the systemic circulation. This study considered whether inhibition of endogenous NO synthase would increase the potency of nitrovasodilators, but not of cyclic adenosine monophosphate-dependent vasodilators, in the pulmonary vasculature. Methods We used the isolated buffer-perfused rabbit lung. Preparations were randomized to receive either pretreatment with NG-nitro-L-arginine methyl ester (or L-NAME, an inhibitor of endogenous NO synthase) or no pretreatment. Stable pulmonary hypertension was then produced by infusing the thromboxane A2 analog U46619. The dose-response characteristics of two nitrovasodilators, sodium nitroprusside and nitroglycerin, and two nonnitrovasodilators, prostaglandin E2 and 5'-N-ethylcarboxamidoadenosine, were studied. Results Inhibition of endogenous NO synthase caused no significant changes in baseline pulmonary artery pressure but did significantly reduce the U46619 infusion rate required to produce pulmonary hypertension. Pretreatment with L-NAME (vs. no L-NAME) resulted in significantly lower values of the log median effective dose with sodium nitroprusside and nitroglycerin. In contrast, pretreatment with L-NAME resulted in no changes in the dose-response characteristics of the cyclic adenosine monophosphate-mediated, NO-independent vasodilators prostaglandin E1 and 5'-N-ethylcarboxamidoadenosine. Conclusions These data suggest that endogenous NO synthase is not an important regulator of basal pulmonary tone in this model but is an important modulator of pulmonary vascular responses to vasoconstriction and to nitrovasodilators. The pulmonary vasodilator effects of nitrovasodilators, but not of nonnitrovasodilators, may depend on the level of activity of NO synthase.

Renal effects of nitric oxide synthesis inhibition in cirrhotic rats

1994 ◽  
Vol 267 (6) ◽  
pp. R1454-R1460 ◽  
Author(s):  
N. M. Atucha ◽  
J. Garcia-Estan ◽  
A. Ramirez ◽  
M. C. Perez ◽  
T. Quesada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Excretion ◽  
Renal Plasma Flow ◽  
Tubular Reabsorption ◽  
Nitric Oxide Synthesis ◽  
Important Mediator ◽  
Experimental Liver Cirrhosis ◽  
Endogenous Nitric Oxide ◽  
And Control ◽  
Experimental Liver

In the present study, we have characterized the renal response to inhibition of endogenous nitric oxide (NO) synthesis [intravenous NG-nitro-L-arginine methyl ester (L-NAME) for 3 h] in anesthetized cirrhotic rats, with (ASC) and without (CIR) ascites, at doses that do not change blood pressure (BP). Administration of L-NAME induced opposite effects on water (UV) and sodium (UNaV) excretion in cirrhotic and control animals. Infusion of 1 microgram.kg-1.min-1 of L-NAME in CIR (n = 5) decreased renal plasma flow (RPF) at the end of the 3-h period, whereas UV, UNaV, and glomerular filtration rate (GFR) were unaltered. In contrast, infusion of L-NAME at 10 micrograms.kg-1.min-1 in six more CIR increased UV and UNaV significantly by the 1st h, without changes in BP or GFR, and these parameters remained elevated throughout the experiment. Infusion of 1 microgram.kg-1.min-1 in ASC (n = 6) did not change BP or GFR but significantly enhanced UV and UNaV after the 1st h. These effects were prevented by pretreatment with L-arginine (0.1 mg.kg-1.min-1) in another group of ASC infused with 1 microgram.kg-1.min-1 of L-NAME. These results indicate that, in ASC and CIR cirrhotic rats, inhibition of NO synthesis at nonpressor does improves renal excretion of sodium and water via a decrease in tubular reabsorption. NO is an important mediator of the renal excretory and hemodynamic alterations of experimental liver cirrhosis.

l-Arginine promotes angiogenesis in the chronically hypoxic lung: a novel mechanism ameliorating pulmonary hypertension

2009 ◽  
Vol 296 (6) ◽  
pp. L1042-L1050 ◽  
Author(s):  
K. Howell ◽  
C. M. Costello ◽  
M. Sands ◽  
I. Dooley ◽  
P. McLoughlin
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Vascular Resistance ◽  
Structural Changes ◽  
Lumen Diameter ◽  
Vascular Lumen ◽  
Arteriolar Resistance ◽  
Endogenous Nitric Oxide ◽  
Alveolar Hypoxia ◽  
Arginine Supplementation

Chronic alveolar hypoxia, whether due to residence at high altitude or lung disease, leads to a sustained increase in pulmonary vascular resistance and pulmonary hypertension (PH). Strategies that augment endogenous nitric oxide production or activity, including l-arginine supplementation, attenuate the development of PH. This action has been attributed to inhibition of vessel wall remodeling, thus preventing structural narrowing of the vascular lumen. However, more recent evidence suggests that structural changes are not responsible for the elevated vascular resistance observed in chronic hypoxic PH, calling into question the previous explanation for the action of l-arginine. We examined the effect of dietary l-arginine supplementation on pulmonary vasoconstriction, structurally determined maximum vascular lumen diameter, and vessel length in rats during 2 wk of exposure to hypoxia. l-Arginine attenuated the development of hypoxic PH by preventing increased arteriolar resistance. It did not alter mean maximal vascular lumen diameter, nor did it augment nitric oxide-mediated vasodilatation, in chronically hypoxic lungs. However, the total length of vessels within the gas exchange region of the hypoxic lungs was significantly increased after l-arginine supplementation. These findings suggest that dietary l-arginine ameliorated hypoxic PH, but not by an effect on the structurally determined lumen diameter of pulmonary blood vessels. l-Arginine enhanced angiogenesis in the hypoxic pulmonary circulation, which may attenuate hypoxic PH by producing new parallel vascular pathways through the lung.

Does Group B Streptococcal Sepsis Attenuate Endogenous Nitric Oxide Synthesis in Neonates?

PEDIATRICS ◽  
1999 ◽  
Vol 103 (6) ◽  
pp. 1313.2-1313
Author(s):  
Akihiko Endo ◽  
Ken Masunaga ◽  
Mamoru Ayusawa ◽  
Michiyoshi Minato ◽  
Masaaki Takada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthesis ◽  
Endogenous Nitric Oxide ◽  
Streptococcal Sepsis ◽  
Group B

scholarly journals Endogenous Nitric Oxide Synthesis Inhibitor Asymmetric Dimethyl l -Arginine Accelerates Endothelial Cell Senescence

2004 ◽  
Vol 24 (10) ◽  
pp. 1816-1822 ◽  
Author(s):  
Fortunato Scalera ◽  
Jürgen Borlak ◽  
Bibiana Beckmann ◽  
Jens Martens-Lobenhoffer ◽  
Thomas Thum ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Cell Senescence ◽  
Nitric Oxide Synthesis ◽  
Synthesis Inhibitor ◽  
Endogenous Nitric Oxide
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