Pulmonary vasodilatory action of endogenous atrial natriuretic factor in rats with hypoxic pulmonary hypertension. Effects of monoclonal atrial natriuretic factor antibody.

Raffestin, Bernadette; Levame, M; Eddahibi, Saadia; Viossat, Isabelle; Braquet, P.; Chabrier, P; Cantin, M.; Adnot, Serge

doi:10.1161/01.res.70.1.184

Cited by 29 publications

(20 citation statements)

References 23 publications

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“…Infusion period ANP-3 Recovery baseline serum irANP levels were mildly elevated at 23 (15) pmol/l compared with the levels of less than 12 pmol/l found by our assay in normal subjects. Infusion of ANP was associated with a dose related increase in plasma irANP levels up to concentrations previously found in patients with severe pulmonary hypertension.…”

Section: Anp-2contrasting

confidence: 65%

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Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease.

Rogers

Sheedy

Waterhouse

et al. 1994

Thorax

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Background -Pulmonary artery pressure is elevated in patients with advanced chronic obstructive pulmonary disease (COPD). Release of atrial natriuretic peptide (ANP) is increased in pulmonary hypertension and this hormone may both selectively vasodilate pulmonary vessels and inhibit pulmonary vascular remodelling. The hypothesis that ANP has a physiological role in protection of the pulmonary circulation from pressure overload, and that it may be beneficial in patients with COPD, has been examined. Methods -Ten patients with hypoxic COPD were infused for 30 minute periods with saline followed by ANP at 0-4, 2, and 10 pmol/kg/min respectively via a pulmonary artery catheter whilst monitoring haemodynamics and oxygenation. Results -Levels of immunoreactive ANP (irANP) increased from a mean (SD) of 23 (15) pmol/l to a maximum of 94 (41) pmol/l. Neither systemic blood pressure, cardiac output nor total systemic vascular resistance showed any correlation with irANP levels. There were negative correlations between levels of ANP and mean pulmonary artery pressure which fell from 28-7 to 25 9 mm Hg, pulmonary artery wedge pressure which fell from 6 5 to 4-6 mm Hg, and total pulmonary vascular resistance which fell from 489 to 428 dynes s cm -5. There was a small fall in Paco2 from 6-2 to 5-9 kPa, whilst venous admixture and oxygen delivery both increased non-significantly. Conclusions -At these pathophysiological concentrations there was evidence that ANP selectively reduced right ventricular afterload. These data support the hypotheses that increased plasma levels of ANP may be beneficial in hypoxic COPD, and that endogenous ANP may ameliorate pulmonary hypertension in humans. (Thorax 1994;49:233-239) Pulmonary vascular resistance is elevated in patients with advanced chronic obstructive pulmonary disease (COPD)l associated with a progressive vascular remodelling of small pulmonary arteries and arterioles,2 although many other factors also contribute. As a result of increased afterload on the right ventricle, stroke volume and ejection fraction are depressed; cardiac output is maintained by a relative tachycardia.3 Oedema occurs during episodes of acute-on-chronic respiratory failure, a syndrome commonly known as "hypoxic cor pulmonale." This is an important step in the natural history of the disease: without treatment 65% of patients die within five years of the first episode.4The role of vasodilators is controversial.56 There have been several short and medium term trials of vasodilator treatment in the condition,7-'2 reviewed by Howard.5 Effects on arterial blood gases and cardiac output have been variable. Most agents have caused greater reduction of systemic than pulmonary vascular resistance. Some longer term trials have found that the pulmonary hypotensive effect disappeared with time, whilst others have found continued benefit at one year. No effect on prognosis has yet been shown.There are three lines of evidence to suggest that atrial natriuretic peptide (ANP) may be helpful in patients with advanc...

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Section: Anp-2contrasting

confidence: 65%

“…It was then diluted to 2 nmol/ml in a solution of 50% normal saline (Baxter, Thetford) and 50% Haemaccel (Hoechst, Hounslow, Middlesex) to minimise adsorption of ANP to surfaces. Vials containing 15 ml of the solution were frozen at -20°C until used.…”

Section: Methodsmentioning

confidence: 99%

Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease.

Rogers

Sheedy

Waterhouse

et al. 1994

Thorax

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“…In this study, the second phase generated much less wall tension, but this was more than adequate to close the vessel lumen. Calculated equivalent intramural pressures of the second phase were 9.0 kPa (68 mmHg) and 9.6 kPa (72 mmHg) in C and CH vessels, respectively [12]. Unfortunately, the response to ANP was not helpful in separating these two phases since it was highly potent against both.…”

Section: Discussionmentioning

confidence: 99%

“…In the isolated lung and in isolated vessels, ANP has been shown to cause vasodilatation when tone is increased by pharmacological means [5][6][7][8][9][10]. The most important physiological vasoconstrictor of the pulmonary circulation is hypoxia and the effect of ANP on hypoxic pulmonary vasoconstriction (HPV) has been studied in anaesthetized animals [6,11,12] and using isolated lung preparations [10]. Until recently, it had proved difficult to demonstrate consistent HPV in isolated pulmonary arteries.…”

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confidence: 99%

Inhibition of hypoxic pulmonary vasoconstriction in isolated rat resistance arteries by atrial natriuretic peptide

Rogers¹,

Thompson²,

Morice³

1997

Eur Respir J

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Atrial natriuretic peptide (ANP) is a vasodilator secreted by the heart in response to right atrial stretch. We have hypothesized that ANP may be released to attenuate pulmonary hypertension due to hypoxia. We have examined whether ANP inhibits hypoxic pulmonary vasoconstriction (HPV) in isolated pulmonary resistance vessels (PRV) from chronically hypoxic (CH) rats, compared to airbreathing, control (C) rats.After at least 17 days of chronic hypoxia, vessels (n=29) were dissected from CH and C littermates and mounted in an automated myograph. The inhibitory effect of ANP on the rapid first contractile phase of HPV, and the relaxant effect of ANP on vessels tonically contracted in the second phase of HPV, were studied.ANP caused concentration-dependent inhibition of HPV in both C and CH vessels (p<0.001), whilst vehicle had no effect (mean maximum inhibition was 88 and 101%, respectively, at 17 nM ANP). ANP also caused significant concentrationdependent relaxation of the second contractile phase of HPV, which was similar in C and CH vessels (mean maximum relaxation of 89 and 94%, respectively; median effective concentrations were 2.4 and 2.0 nM, respectively).We conclude that atrial natriuretic peptide is a potent antagonist of both contractile phases of hypoxic pulmonary vasoconstriction in isolated rat pulmonary resistance vessels at concentrations similar to those observed in hypoxic pulmonary hypertension in life. There was no difference between vessels from chronically hypoxic and control animals. Eur Respir J 1997; 10: 2061-2065 We have hypothesized that the cardiac hormone, atrial natriuretic peptide (ANP), may be released to attenuate pulmonary hypertension due to hypoxia. We have examined whether ANP inhibits hypoxic pulmonary vasoconstriction (HPV) in isolated pulmonary resistance vessels.ANP is a vasodilator of the pulmonary vasculature hypothesized to have a physiological role in modulating pulmonary vascular resistance. Release of ANP is governed by right atrial stretch and because of its short half-life, intravascular concentrations are highest in the pulmonary circulation. ANP is elevated in conditions characterized by pulmonary hypertension. Levels are modestly increased in chronic obstructive pulmonary disease (COPD) and more markedly in severe pulmonary hypertension [1][2][3][4]. In patients with COPD we have demonstrated that infusion of ANP leads to a fall in mean pulmonary artery pressure, pulmonary artery wedge pressure and total pulmonary vascular resistance, without significant effects on the systemic vasculature [4].The normal pulmonary vasculature has low intrinsic tone and to demonstrate the vasodilator properties of ANP precontraction is required. In the isolated lung and in isolated vessels, ANP has been shown to cause vasodilatation when tone is increased by pharmacological means [5][6][7][8][9][10]. The most important physiological vasoconstrictor of the pulmonary circulation is hypoxia and the effect of ANP on hypoxic pulmonary vasoconstriction (HPV) has been studied in a...

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“…The ANP hormone leads to pulmonary vasodilatation, and might therefore, counteract pulmonary hypertension and right heart hypertrophy in hypoxic organisms [8,[14][15][16][17][18]. In patients with chronic obstructive lung disease (COLD), ANP infusion lowered the pulmonary artery pressure [19].…”

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confidence: 99%

Atrial natriuretic peptide in acute hypoxia-exposed healthy subjects and in hypoxaemic patients

Lordick¹,

Hauck²,

Senekowitsch³

et al. 1995

Eur Respir J

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Plasma atrial natriuretic peptide (ANP) is an endogenous vasodilator, which might counteract pulmonary hypertension due to hypoxaemia. The aim of this study was to investigate the influence of acute and chronic hypoxia on plasma (ANP) concentrations in humans. Venous plasma ANP concentrations in six healthy subjects were measured before and after inhalation of hypoxic air (11% O2) at rest for 30 min, and following 5 min of mild hypoxic exercise (25 W). Pulmonary arterial plasma ANP levels were determined in 31 right heart catheterized patients with lung disease. In healthy subjects, mean arterial oxygen tension (Pao2) was 6.8 +/- 1.9 kPa after 30 min hypoxia at rest, and 4.7 +/- 0.9 kPa after hypoxic exercise testing. Hypoxia at rest did not induce significant changes in ANP concentrations, whereas hypoxic exercise led to significantly increased ANP levels. Among hypoxaemic patients, significantly elevated plasma ANP levels were found only in the subgroup with increased mean pulmonary artery pressure, but not in the subgroup with normal pulmonary artery pressure. In summary, severe acute hypoxia induced by hypoxic exercise, but not moderate acute hypoxia at rest, leads to increased ANP levels in healthy subjects. Chronic hypoxia alone does not lead to elevated plasma ANP levels; whereas, hypoxia combined with pulmonary hypertension causes increased plasma ANP concentrations in diseased subjects.

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Pulmonary vasodilatory action of endogenous atrial natriuretic factor in rats with hypoxic pulmonary hypertension. Effects of monoclonal atrial natriuretic factor antibody.

Cited by 29 publications

References 23 publications

Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease.

Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease.

Inhibition of hypoxic pulmonary vasoconstriction in isolated rat resistance arteries by atrial natriuretic peptide

Atrial natriuretic peptide in acute hypoxia-exposed healthy subjects and in hypoxaemic patients

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