Effect of chronic hypoxia on rat pulmonary resistance vessels: vasodilatation by atrial natriuretic peptide

Rogers, Trevor; Stewart, Andrew M.; Morice, Alyn H.

doi:10.1042/cs0830723

Cited by 22 publications

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“…We chose eight hours of hypoxia during the light period to coincide with the major sleep period of the rat. This paradigm has been shown by others to result in prototypic hypoxic responses, increases in hematocrit, pulmonary artery pressure, and right ventricular hypertrophy-a finding we found and confirmed in one strain [13][14][15]22].…”

Section: Discussionsupporting

confidence: 62%

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Constant daily hypoxia leads to different degrees of pulmonary hypertension in two different rat strains

Bouserhal¹,

Lunteren²,

Jacono³

2012

OJMIP

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Pulmonary diseases associated with diurnal hypoxemia are known to be associated with pulmonary hypertension in some patients. In this study we examined the effects of daily hypoxia (10% oxygen; 8h/day for 14 days) on two strains of rats to simulate sleep related hypoxia in pulmonary diseases expecting to find differences in vascular responses, the development of right ventricular hypertrophy and pulmonary hypertension according to genetic background. In response to daily hypoxia, Sprague Dawley rats developed right ventricular hypertrophy while Brown Norway rats did not. Both strains developed pulmonary hypertension (elevated right ventricular pressure) although the increase was significantly greater in the Sprague Dawley strain. Pulmonary artery (first branch) vasoconstrictive responses to potassium chloride were increased equally in both strains and the subsequent vasodilation with acetylcholine were reduced equally with daily hypoxia in both strains. Taken together, these findings suggest that the genetic makeup of the rats contributed significantly to the development of right ventricular hypertrophy and the degree of pulmonary hypertension. Moreover, this response is not secondary to differences in the intralobar pulmonary vascular reactivity. Genetic background could explain why certain patients do worse with hypoxia inducing pulmonary vascular diseases.

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Section: Discussionsupporting

confidence: 62%

“…As described previously, 2 mm long pulmonary artery rings were dissected from the right and left first branch pulmonary arteries and suspended at 17.5 mmHg [15]. Maximum contraction was determined with exposure to 80 mM of KCL and calculated in grams of force per gram of tissue.…”

Section: In Vitro Measurement Of Contractility Of Pulmonary Artery Ringsmentioning

confidence: 99%

Constant daily hypoxia leads to different degrees of pulmonary hypertension in two different rat strains

Bouserhal¹,

Lunteren²,

Jacono³

2012

OJMIP

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“…The technique of wire myography is commonly utilised for vascular reactivity studies and has been described in detail elsewhere (28). Briefly, vessels were mounted on two 40 mm stainless steel wires in the jaws of an automated wire myograph (Cambustion Ltd, Cambridge, Cambridgshire, UK), the myograph bath filled with physiological saline solution (PSS) heated to 37 8C and bubbled with 95% O 2 /5% CO 2 to maintain a physiological pH of 7.4.…”

Section: Tfm Mouse Colonymentioning

confidence: 99%

Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse

Jones

Pugh²,

Hall³

et al. 2003

European Journal of Endocrinology

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Objective: Testicular feminised (Tfm) mice express a non-functional androgen receptor, and also have reduced levels of circulating testosterone. Recent studies support a cardio-protective role for testosterone since it elicits systemic and pulmonary vasodilatation. The aim of the present study was to determine whether androgen insensitivity and hypotestosteronaemia in the Tfm mouse are associated with abnormal vascular reactivity or hormone status. Methods: Adult male Tfm and littermate control mice were killed and the blood collected. Femoral (diameter range = 183 -508 mm) and pulmonary (diameter range = 320-816 mm) arteries were dissected and loaded in either a wire or pressure myograph, at 100 mmHg or 17.5 mmHg respectively. Pharmacological assessment of the vasoreactivity to potassium chloride (KCl, 80 mmol/l) and either noradrenaline (NA, 1 nmol/l -100 mmol/l) and acetylcholine (ACh, 0.1 -100 mmol/l) or testosterone (1 nmol/l -100 mmol/l) was then made. Results: Tfm mice had reduced levels of testosterone (1.8^0.3 nmol/l) compared with controls (9.3^2.0 nmol/l, P , 0:001Þ and elevated levels of cholesterol (3.6+0.1 mmol/l) compared with controls ð3:2 þ 0:1 mmol=l; P , 0:05Þ: Femoral arteries from Tfm mice exhibited reduced vasoconstriction to 80 mmol/l KCl ð3:27^0:23 mN=mmÞ compared with vessels from controls ð4:44^0:41 mN=mm; P , 0:05Þ; and reduced endothelial-dependent vasodilatation to 0.1-100 mmol/l ACh ð23:3^3:6% relaxation) compared with vessels from controls ð41:6^5:4% relaxation, P , 0:05Þ: Vasoconstriction to NA (1 nmol/l -100 mmol/l) and vasodilatation to testosterone were unaffected. Conclusions: Androgen receptor deficiency and hypotestosteronaemia in the Tfm mouse reduced endothelial function and impaired voltage-operated calcium channel activity, which may pre-dispose to cardiovascular disease. Testosterone-induced vasodilatation was unaffected, demonstrating no involvement of the androgen receptor in this response.

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“…In support of this, plasma levels of ANP have been shown to be elevated in response to increased pulmonary artery pressure both in animal models (McKenzie et al, 1986;Jin et al, 1990) and in man (Winter et al, 1989;Morice et al, 1990). The vasodilatation caused by ANP is particularly potent in the pulmonary circulation (Jansen et al, 1987) with hypoxic vasoconstriction being preferentially inhibited (Rogers et al, 1992). In a recent study we have shown that an acute infusion of ANP in patients with COAD and pulmonary hypertension caused specific pulmonary vasodilatation without adversely effecting systemic haemodynamics or ventilation perfusion matching (Rogers et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Jansen et al (1987) showed that ANP was more potent in isolated pulmonary, as opposed to renal, vessels of the pig. We have demonstrated that ANP causes a dose-dependent relaxation in preconstricted isolated perfused lungs (Stewart et al, 1991b), and isolated pulmonary resistance vessels (Rogers et al, 1992) in the rat and that relaxation appears to be particularly potent against hypoxic vasoconstriction (Rogers et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Neutral endopeptidase (NEP) inhibition in rats with established pulmonary hypertension secondary to chronic hypoxia

Thompson

Sheedy

Morice

1994

British J Pharmacology

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1Atrial natriuretic peptide (ANP) causes vasorelaxation in the pulmonary vasculature. ANP levels are elevated in conditions characterized by pulmonary hypertension and it has been hypothesized that ANP may be autoregulatory in the pulmonary circulation. 2 One route of ANP metabolism in vivo is by the action of the enzyme neutral endopeptidase (NEP). We have studied the effects of the NEP inhibitor, SCH 42495, in rats with established pulmonary hypertension secondary to chronic hypoxia. 3 Rats (n = 32) were divided into 4 groups. Normoxic controls were kept in air for 10 days (NClO) and all other animals were placed in a normobaric hypoxic chamber (Fi 02 10%). Chronic hypoxic controls were studied at 10 days (CHC10). After 10 days hypoxia the two remaining groups received oral treatment for a further 10 days, consisting of either SCH 42495 (30 mg kg-', twice daily CHT20) or methyl cellulose vehicle (0.4%, twice daily, CHV20). 4 Animals were anaesthetized and blood collected for measurement of plasma ANP. Hearts were dissected and ventricles weighed and the histology of the pulmonary vasculature examined. 5 CHClO rats had significant right ventricular hypertrophy (0.53 ± 0.08) and pulmonary vascular remodelling (29.0 0.01%) and had gained significantly less body weight (33.2 ± 5.5 g) than NC1O rats (0.31 ± 0.04, 10.9 0.01%, and 59.2 ± 11.9 g respectively). CHC1O rats had significantly elevated plasma ANP levels (58.4 ± 9.9 pM) compared with NClO rats (23.9 ± 32 pM). Treatment with SCH 42495 caused a significant reduction in pulmonary vascular remodelling (25.0 ± 0.01%) and right ventricular hypertrophy (0.52 ± 0.09) in CHT20 rats compared with CHV20 controls (33.0 ± 0.02% and 0.61 ± 0.09 respectively). Pulmonary vascular remodelling was also significantly lower in CHT20 rats than CHC1O animals. 6 Thus, short term inhibition of NEP causes regression of established pulmonary vascular remodelling and may be a useful therapeutic strategy in pulmonary hypertension.

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Effect of chronic hypoxia on rat pulmonary resistance vessels: vasodilatation by atrial natriuretic peptide

Cited by 22 publications

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Constant daily hypoxia leads to different degrees of pulmonary hypertension in two different rat strains

Constant daily hypoxia leads to different degrees of pulmonary hypertension in two different rat strains

Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse

Neutral endopeptidase (NEP) inhibition in rats with established pulmonary hypertension secondary to chronic hypoxia

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