Interaction between endogenous nitric oxide and carbon mon-oxide in the pathogenesis of hypoxic pulmonary hypertension

2003 ◽  
Vol 48 (1) ◽  
pp. 86 ◽  
Author(s):  
Yun SHI
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Hypoxic Pulmonary Hypertension ◽  
Endogenous Nitric Oxide

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.

scholarly journals Protective Role of Myelocytic Nitric Oxide Synthases in Hypoxic Pulmonary Hypertension in Mice

2018 ◽  
Vol WCP2018 (0) ◽  
pp. OR20-1
Author(s):  
Masato Tsutsui ◽  
Takaaki Ogoshi ◽  
Takashi Kido ◽  
Sohsuke Yamada ◽  
Ke-Yong Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Protective Role ◽  
Nitric Oxide Synthases ◽  
Hypoxic Pulmonary Hypertension

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.

Sustained therapeutic hypercapnia attenuates pulmonary arterial Rho-kinase activity and ameliorates chronic hypoxic pulmonary hypertension in juvenile rats

2012 ◽  
Vol 302 (12) ◽  
pp. H2599-H2611 ◽  
Author(s):  
Gary Peng ◽  
Julijana Ivanovska ◽  
Crystal Kantores ◽  
Todd Van Vliet ◽  
Doreen Engelberts ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Right Ventricular ◽  
Rho Kinase ◽  
Juvenile Rats ◽  
Hypoxic Pulmonary Hypertension ◽  
Rescue Treatment ◽  
Pulmonary Arterial ◽  
Rock Activity

Sustained therapeutic hypercapnia prevents pulmonary hypertension in experimental animals, but its rescue effects on established disease have not been studied. Therapies that inhibit Rho-kinase (ROCK) and/or augment nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling can reverse or prevent progression of chronic pulmonary hypertension. Our objective in the present study was to determine whether sustained rescue treatment with inhaled CO2 (therapeutic hypercapnia) would improve structural and functional changes of chronic hypoxic pulmonary hypertension. Spontaneously breathing pups were exposed to normoxia (21% O2) or hypoxia (13% O2) from postnatal days 1–21 with or without 7% CO2 (PaCO2 elevated by ∼25 mmHg) or 10% CO2 (PaCO2 elevated by ∼40 mmHg) from days 14 to 21. Compared with hypoxia alone, animals exposed to hypoxia and 10% CO2 had significantly ( P < 0.05) decreased pulmonary vascular resistance, right-ventricular systolic pressure, right-ventricular hypertrophy, and medial wall thickness of pulmonary resistance arteries as well as decreased lung phosphodiesterase (PDE) V, RhoA, and ROCK activity. Rescue treatment with 10% CO2, or treatment with a ROCK inhibitor (15 mg/kg ip Y-27632 twice daily from days 14 to 21), also increased pulmonary arterial endothelial nitric oxide synthase and lung NO content. In contrast, cGMP content and cGMP-dependent protein kinase (PKG) activity were increased by exposure to 10% CO2, but not by ROCK inhibition with Y-27632. In vitro exposure of pulmonary artery smooth muscle cells to hypercapnia suppressed serum-induced ROCK activity, which was prevented by inhibition of PKG with Rp-8-Br-PET-cGMPS. We conclude that sustained hypercapnia dose-dependently inhibited ROCK activity, augmented NO-cGMP-PKG signaling, and led to partial improvements in the hemodynamic and structural abnormalities of chronic hypoxic PHT in juvenile rats. Increased PKG content and activity appears to play a major upstream role in CO2-induced suppression of ROCK activity in pulmonary arterial smooth muscle.

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