Atrial natriuretic peptide-induced relaxation of pre-constricted isolated rat perfused lungs: A comparison in control and hypoxia-adapted animals

1991 ◽  
Vol 81 (2) ◽  
pp. 201-208 ◽  
Author(s):  
A. G. Stewart ◽  
J. S. Thompson ◽  
T. K. Rogers ◽  
A. H. Morice
Keyword(s):  
Pulmonary Artery ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Pulmonary Artery Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Prostaglandin F2α ◽  
Artery Pressure ◽  
Pulmonary Vasoconstriction ◽  
Dose Dependent ◽  
Atrial Natriuretic

1. To further understand the vasodilator actions of atrial natriuretic peptide and its role in hypoxic pulmonary hypertension, we studied the effects of atrial natriuretic peptide in the isolated perfused rat lung during normoxic ventilation and after elevation of pulmonary artery pressure by either hypoxic ventilation or infusion of prostaglandin F2α. Control animals were compared with littermates that had become adapted to a 10% O2 environment for 3 weeks. Atrial natriuretic peptide was compared with atriopeptin I and atriopeptin III in order to study its structure-activity relationship. 2. Five experiments, each involving six control and six chronically hypoxic rats, were performed. During normoxic ventilation, atrial natriuretic peptide (30 ng-3 μg) produced a dose-dependent reduction in pulmonary artery pressure in chronically hypoxic rats, but had no action in the control animals. 3. Atrial natriuretic peptide dose-dependently abolished hypoxic pulmonary vasoconstriction to a greater extent in chronically hypoxic rats (EC50 98 ng) than in control rats (EC50 298 ng; P < 0.001). Bolus atrial natriuretic peptide (100 ng) produced a plasma concentration of 22.6 pmol/l at 1 min, which is within the pathophysiological range. Initial plasma atrial natriuretic peptide levels were 9.4 pmol/l in control animals and 27.4 pmol/l in chronically hypoxic rats. 4. Chronically hypoxic rats were more sensitive to atriopeptin I, atriopeptin III and atrial natriuretic peptide than were the control rats (P < 0.05). Atrial natriuretic peptide and atriopeptin III were equipotent and were 10 times more potent than atriopeptide I in both groups (P < 0.001). 5. Although atrial natriuretic peptide lowered pulmonary artery pressure in isolated perfused lungs pre-constricted with prostaglandin F2α (5 μg/min), there was no difference between the control and chronically hypoxic groups, and the EC50 296 ng in the chronically hypoxic rats was significantly (P < 0.001) less than that seen in the chronically hypoxic despite similar levels of induced constriction by the two stimuli. 6. A set dose of atrial natriuretic peptide produced the same percentage reduction in hypoxic pulmonary vasoconstriction despite differing levels of pre-constriction produced by ventilating with 7%, 5%, 3% or 0% O2. There was no change in the arterial partial pressure of O2 or the alveolar-arterial gradient after injection of atrial natriuretic peptide, suggesting that its effects are not due to a reduction in pulmonary oedema. 7. Atrial natriuretic peptide relaxes pre-constricted pulmonary arteries in the isolated perfused rat lung in a dose-dependent manner within the pathophysiological range. The greater action of atrial natriuretic peptide in chronic hypoxia could be due to its action at the new sites of hypoxic pulmonary vasoconstriction, the newly muscularized alveolar arteries which develop during adaptation to hypoxia.

Effects of continuous infusion of atrial natriuretic peptide on the pulmonary hypertension induced by chronic hypoxia in rats

1991 ◽  
Vol 81 (3) ◽  
pp. 379-385 ◽  
Author(s):  
L. Zhao ◽  
R. J. D. Winter ◽  
T. Krausz ◽  
J. M. B. Hughes
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Pulmonary Artery Pressure ◽  
Chronic Hypoxia ◽  
Systemic Blood Pressure ◽  
Artery Pressure ◽  
Pulmonary Vascular Remodelling ◽  
Atrial Natriuretic

1. The effects of the continuous infusion of atrial natriuretic peptide on the development of pulmonary hypertension were studied in rats exposed to chronic hypoxia. 2. Continuous intravenous infusion of two doses of synthetic rat atrial natriuretic peptide, 300 ng/h per rat (0.10 pmol/h per rat) and 800 ng/h per rat (0.28 pmol/h per rat), attenuated the development of pulmonary hypertension in rats exposed to chronic hypoxia (fractional concentration of oxygen in inspired air = 10%) for 7 days: (i) the pulmonary artery pressure (mean ± sd) in the vehicle-treated hypoxic group was 45 ± 6 mmHg compared with 28 ± 6 mmHg in the vehicle-treated normotoxic group (n = 8, P < 0.001); (ii) treatment with atrial natriuretic peptide in normoxia did not alter the pulmonary artery pressure, systemic blood pressure or heart rate; (iii) treatment with atrial natriuretic peptide in hypoxia resulted in a lower pulmonary artery pressure in the group treated with 800 ng of atrial natriuretic peptide/h per rat (38 ± 8 mmHg, P < 0.05 compared with the vehicle-treated hypoxic group) without affecting the systemic blood pressure or heart rate. 3. Chronic hypoxia resulted in an extension of vascular smooth muscle towards the periphery of the lung with the development of muscle in normally non-muscularized vessels (remodelling). Quantitative assessment of the small pulmonary vessels (external diameter 25–55 μm) showed that atrial natriuretic peptide treatment reduced pulmonary vascular remodelling in hypoxia (the percentage of thick-walled vessels in the peripheral lung hypoxic vehicle-treated group was 25 ± 6 compared with 19 ± 4 in the group given 300 ng of atrial natriuretic peptide/h per rat and 17 ± 7 in the group given 800 ng of atrial natriuretic peptide/h per rat, means ± sd, both P < 0.01 compared with the vehicle-treated normoxic group). 4. These data show that infusion of synthetic atrial natriuretic peptide attenuated the pulmonary vascular remodelling and associated pulmonary hypertension produced by chronic hypoxia.

Vasopressin Lowers Pulmonary Artery Pressure in Hypoxic Rats by Releasing Atrial Natriuretic Peptide

1989 ◽  
Vol 298 (4) ◽  
pp. 227-236 ◽  
Author(s):  
Hongkui Jin ◽  
Yiu-Fai Chen ◽  
Ren-Hui Yang ◽  
Robert M. Jackson ◽  
Suzanne Oparil ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Pulmonary Artery Pressure ◽  
Artery Pressure ◽  
Atrial Natriuretic

Pulmonary vasodilation by acetazolamide during hypoxia is unrelated to carbonic anhydrase inhibition

2007 ◽  
Vol 292 (1) ◽  
pp. L178-L184 ◽  
Author(s):  
Claudia Höhne ◽  
Philipp A. Pickerodt ◽  
Roland C. Francis ◽  
Willehad Boemke ◽  
Erik R. Swenson
Keyword(s):  
Carbonic Anhydrase ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Pulmonary Artery Pressure ◽  
Vascular Resistance ◽  
Low Dose ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Artery Pressure ◽  
Pulmonary Vasoconstriction ◽  
Mean Pulmonary Artery Pressure

Acute hypoxic pulmonary vasoconstriction can be inhibited by high doses of the carbonic anhydrase inhibitor acetazolamide. This study aimed to determine whether acetazolamide is effective at dosing relevant to human use at high altitude and to investigate whether its efficacy against hypoxic pulmonary vasoconstriction is dependent on carbonic anhydrase inhibition by testing other potent heterocyclic sulfonamide carbonic anhydrase inhibitors. Six conscious dogs were studied in five protocols: 1) controls, 2) low-dose intravenous acetazolamide (2 mg·kg−1·h−1), 3) oral acetazolamide (5 mg/kg), 4) benzolamide, a membrane-impermeant inhibitor, and 5) ethoxzolamide, a membrane-permeant inhibitor. In all protocols, unanesthetized dogs breathed spontaneously during the first hour (normoxia) and then breathed 9–10% O2 for the next 2 h. Arterial oxygen tension ranged between 35 and 39 mmHg during hypoxia in all protocols. In controls, mean pulmonary artery pressure increased by 8 mmHg and pulmonary vascular resistance by 200 dyn·s·cm−5 ( P <0.05). With intravenous acetazolamide, mean pulmonary artery pressure and pulmonary vascular resistance remained unchanged during hypoxia. With oral acetazolamide, mean pulmonary artery pressure increased by 5 mmHg ( P < 0.05), but pulmonary vascular resistance did not change during hypoxia. With benzolamide and ethoxzolamide, mean pulmonary artery pressure increased by 6–7 mmHg and pulmonary vascular resistance by 150–200 dyn·s·cm−5 during hypoxia ( P < 0.05). Low-dose acetazolamide is effective against acute hypoxic pulmonary vasoconstriction in vivo. The lack of effect with two other potent carbonic anhydrase inhibitors suggests that carbonic anhydrase is not involved in the mediation of hypoxic pulmonary vasoconstriction and that acetazolamide acts on a different receptor or channel.

Effect of hypoxia on pulmonary artery pressure of dogs

1964 ◽  
Vol 207 (6) ◽  
pp. 1314-1318 ◽  
Author(s):  
Benson R. Wilcox ◽  
W. Gerald Austen ◽  
Harvey W. Bender
Keyword(s):  
Pulmonary Artery ◽  
Arterial Pressure ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Arterial Pressure ◽  
Venous Pressure ◽  
Artery Pressure ◽  
Pulmonary Vasoconstriction ◽  
Systemic Hypoxia ◽  
Pump Output ◽  
Pulmonary Arterial

The mechanism by which the pulmonary artery pressure rises in response to hypoxia has never been clearly demonstrated. This problem was reinvestigated in experiments utilizing separate pulmonary and systemic perfusion systems. These vascular beds were perfused in such a fashion that a change in pulmonary artery pressure could only result from changes in vasomotor tone. Alveolar-pulmonary vein hypoxia was usually associated with a slight fall in pulmonary artery pressure. Systemic hypoxia resulted in elevation of pulmonary arterial pressure in 10 of the 12 animals tested with a constant-flow and constant-pulmonary venous pressure. In addition, all animals with systemic desaturation showed an increased venous return. When the "cardiac output" (pump output) was increased to match this return, the elevation in pulmonary artery pressure increased. It was concluded that the pulmonary arterial pressure elevation seen with hypoxia is the result of active pulmonary vasoconstriction coupled with an increased pulmonary blood flow.

Effects of atrial natriuretic peptide on isolated bovine mesenteric lymph vessels

1990 ◽  
Vol 259 (1) ◽  
pp. H42-H47 ◽  
Author(s):  
T. Ohhashi ◽  
N. Watanabe ◽  
Y. Kawai
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Smooth Muscles ◽  
Lymphatic Endothelium ◽  
Low Concentration ◽  
Lymph Vessels ◽  
Mesenteric Lymph ◽  
Spontaneous Contractions ◽  
Dose Dependent ◽  
Atrial Natriuretic

The mode of action of atrial natriuretic peptide (ANP) on bovine mesenteric lymphatics was investigated by recording isometric tensions in isolated cylindrical segments. ANP in concentrations from 5 to 30 ng/ml caused dose-related decreases in the rhythm and amplitude of spontaneous contractions. No tachyphylaxis was observed in the ANP-induced responses in lymph vessels. Addition of ANP in a low concentration ranging from 3 to 100 ng/ml produced a dose-dependent relaxation in the lymphatic preparations precontracted by 10(-7) M bradykinin. The ANP-induced relaxation was not modified by pretreatment with 5 x 10(-7) M propranolol, 5 x 10(-7) M atropine, 10(-6) M cimetidine, 5 x 10(-5) M aspirin, or 10(-5) M ouabain. The mechanical rubbing of endothelial cells in the lymph vessels caused no significant effect on the ANP-induced relaxation. The relaxation, however, was significantly reduced by pretreatment with 10(-5) M methylene blue. These results suggest that ANP in a low concentration seems to inhibit lymph transport through a reduction of spontaneous contractions and a marked relaxation of lymphatic smooth muscles in bovine mesenteric lymphatics and that ANP may produce the relaxation through synthesis of guanosine 3',5' cyclic monophosphate, independent of the lymphatic endothelium.

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