Point:Counterpoint: Chronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature

Rabinovitch, Marlene; Chesler, Naomi C.; Molthen, Robert C.

doi:10.1152/japplphysiol.00274.2007

Cited by 25 publications

(15 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6), RV hypertrophy, elevated hematocrit (Table 2), and increased lung volumes (Table 2), as previously reported (12,30,32,33,41,45,49,56,61). In addition, we observed increased total length of the pulmonary vessels, suggesting angiogenesis, a finding supported by recent reports (5,30,32,57), although others have reported loss of pulmonary vessels in this condition, as recently reviewed (39,40,60).…”

Section: Discussionsupporting

confidence: 90%

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

Howell

Costello

Sands³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

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

Howell

Costello

Sands³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Loss of precapillary arterioles is known to be involved in the pathogenesis of PH. 19,20 Zhao et al 21 used microangiography to demonstrate a loss of small peripheral pulmonary arteries that had already begun by a very early time point in the monocrotaline rat model, and a "mild rarefaction" or loss of small PAs has been reported in chronically hypoxic mice as well. 22,23 We found evidence of vascular pruning after 3 weeks of SuHx using barium-injected CT angiography.…”

Section: Discussionmentioning

confidence: 99%

The Sugen 5416/Hypoxia Mouse Model of Pulmonary Hypertension Revisited: Long‐Term Follow‐Up

et al. 2014

View full text Add to dashboard Cite

a SHV and GH contributed equally to this work.Abstract: The combination of a vascular endothelial growth factor receptor antagonist, Sugen 5416 (SU5416), and chronic hypoxia is known to cause pronounced pulmonary hypertension (PH) with angioobliterative lesions in rats and leads to exaggerated PH in mice as well. We sought to determine whether weekly SU5416 injections during 3 weeks of hypoxia leads to long-term development of angioobliterative lesions and sustained or progressive PH in mice. Male C57BL/6J mice were injected with SU5416 (SuHx) or vehicle (VehHx) weekly during 3 weeks of exposure to 10% oxygen. Echocardiographic and invasive measures of hemodynamics and pulmonary vascular morphometry were performed after the 3-week hypoxic exposure and after 10 weeks of recovery in normoxia. SuHx led to higher right ventricular (RV) systolic pressure and RV hypertrophy than VehHx after 3 weeks of hypoxia. Ten weeks after hypoxic exposure, RV systolic pressure decreased but remained elevated in SuHx mice compared with VehHx or normoxic control mice, but RV hypertrophy had resolved. After 3 weeks of hypoxia and 10 weeks of followup in normoxia, tricuspid annular plane systolic excursion was significantly decreased, indicating decreased systolic RV function. Very few angioobliterative lesions were found at the 10-week follow-up time point in SuHx mouse lungs. In conclusion, SU5416 combined with 3 weeks of hypoxia causes a more profound PH phenotype in mice than hypoxia alone. PH persists over 10 weeks of normoxic follow-up in SuHx mice, but significant angioobliterative lesions do not occur, and neither PH nor RV dysfunction worsens. The SuHx mouse model is a useful adjunct to other PH models, but the search will continue for a mouse model that better recapitulates the human phenotype.

show abstract

“…Rats exposed to several weeks of simulated high-altitude exhibit substantial increases in P PA and right ventricular mass, accompanied by increased vascular wall thickness, due to PASMC hypertrophy and hyperplasia, and distal muscularization (513,596). While imaging studies initially appeared to suggest that remodeling in these models reduced luminal diameter and resulted in rarefaction, or vascular pruning (263,512), later observations showing that remodeling in this model appears to occur in an outward manner (271) and that administration of ROCK inhibitors acutely normalized P PA (448), suggest that the imaging results may have reflected incomplete reversal of vasoconstriction or variable perfusion (50,406,595). Mice also develop PH upon exposure to CH, although PASMC proliferation is minimal (38,470,596) and remodeling is most often observed as muscularization of distal vessels and thickening and functional stiffening of proximal, conduit arteries (593,594,596).…”

Section: Hypoxiamentioning

confidence: 99%

Lung Circulation

Suresh

Shimoda

2016

Comprehensive Physiology

104

View full text Add to dashboard Cite

The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed.

show abstract

Point:Counterpoint: Chronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature

Cited by 25 publications

References 25 publications

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

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

The Sugen 5416/Hypoxia Mouse Model of Pulmonary Hypertension Revisited: Long‐Term Follow‐Up

Lung Circulation

Contact Info

Product

Resources

About