A bronchial epithelium-derived factor reduces pulmonary vascular tone in the newborn rat

2004 ◽  
Vol 96 (4) ◽  
pp. 1399-1405 ◽  
Author(s):  
J. Belik ◽  
J. Pan ◽  
R. P. Jankov ◽  
A. K. Tanswell
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arteries ◽  
Bronchial Epithelium ◽  
Force Generation ◽  
Phosphatidylinositol 3 Kinase ◽  
Newborn Rat ◽  
No Release ◽  
Phosphatidylinositol 3

The factors accounting for the maintenance of a low pulmonary vascular resistance postnatally are not completely understood. The aim of this study was to test the hypothesis that bronchial epithelium produces a factor capable of relaxing adjacent pulmonary arterial smooth muscle. We studied fourth-generation intralobar pulmonary arteries and bronchi of 4- to 8-day-old rats. Arteries were mounted on a wire myograph, alone or with the adjacent bronchus. The presence of the attached bronchus significantly reduced pulmonary artery force generation induced by the thromboxane analog (U-46619) or KCl whether the endothelium was present or absent ( P < 0.01). The converse was not true in that bronchial force generation was not affected when studied with the adjacent pulmonary artery. Mechanical removal of the bronchial epithelium or addition of the nitric oxide (NO) synthase (NOS) nonspecific ( NG-monomethyl-l-arginine) or the specific neuronal NOS (7-nitroindazole) inhibitors increased arterial force generation to levels comparable to the isolated artery preparation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, significantly decreased ( P < 0.01) NO release of pulmonary arteries only when the adjacent bronchus was present. We conclude that bronchial epithelium in the newborn rat produces a factor capable of lowering pulmonary vascular muscle tone. This relaxant effect can be suppressed by NOS and phosphatidylinositol 3-kinase kinase inhibition, suggesting an action via NOS phosphorylation and NO release. We speculate that such a mechanism may be operative in vivo and plays an important role in control of pulmonary vascular resistance in the early postnatal period.

Large pulmonary arteries and the control of pulmonary vascular resistance in the newborn

1994 ◽  
Vol 72 (11) ◽  
pp. 1464-1468 ◽  
Author(s):  
J. Belik
Keyword(s):  
Mechanical Properties ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arteries ◽  
Isometric Tension ◽  
Force Generation ◽  
Myogenic Response ◽  
Capacitance Vessels

In the immediate neonatal period the pulmonary vascular resistance is higher than later in life. The role of maturational differences in the smooth muscle mechanical properties of large capacitance vessels in this response has not been previously studied. To this end, we studied the smooth muscle isometric and isotonic mechanical properties, as well as the myogenic response of large extralobar pulmonary arteries in newborn and adult guinea pigs. Compared with the adult, the newborn pulmonary vascular smooth muscle generates less force and has a similar shortening capacity but longer isometric and isotonic relaxation half times. The myogenic response could be elicited in 80% of the newborn and 70% of the adult vessels. A 20% increase in vessel diameter resulted in force generation equivalent to 46 + 5.1 % of maximal isometric tension in the newborn. Such a response was significantly greater than observed for the adult vessels (14 ± 2.8%; p < 0.001). Our results showed significant maturational differences in the mechanical properties of the large pulmonary artery smooth muscle in the newborn. We speculate that the presence of myogenic response in large pulmonary capacitance vessels and the observed greater magnitude of stretch-induced force generation in the newborn may play an important role in the maintenance of a higher pulmonary vascular resistance in the neonatal period.Key words: myogenic response, pulmonary artery, newborn.

Vagal control of pulmonary vascular resistance in the turtle Chrysemys scripta

1977 ◽  
Vol 55 (2) ◽  
pp. 359-367 ◽  
Author(s):  
William K. Milsom ◽  
B. Lowell Langille ◽  
David R. Jones
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Sympathetic Innervation ◽  
Pulmonary Arteries ◽  
Lung Parenchyma ◽  
Distal Segment ◽  
Cholinergic Innervation ◽  
Pulmonary Flow ◽  
Induced Changes

We have directly examined the control of pulmonary vascular resistance in the turtle Chrysemys scripta to determine the way in which pulmonary vasoregulation is achieved. The pulmonary circulation of the turtle Chrysemys scripta receives a strong excitatory cholinergic innervation from the vagus nerve. The major site of vasoconstrictor activity is in the extrinsic pulmonary artery proximal to the lung with only weak constrictor activity evident in the intrinsic arteries and arterioles within the lung parenchyma. No cholinergic innervation is evident in the segment of the extrinsic pulmonary artery proximal to the origin of the arterial ligament (ligamentum Botalli) and all vagally induced changes in flow resistance reside in the much narrower segment distal to this site. Vagal stimulation in an intact preparation produces sufficient constriction in the distal segment of extrinsic pulmonary artery to totally occlude pulmonary flow. The pulmonary arteries appear to be devoid of sympathetic innervation.

The peculiarities of pulmonary macro- and microhemodynamics changes after treatment with agonists and blockers of cholinoceptors

2021 ◽  
Vol 20 (4) ◽  
pp. 35-44
Author(s):  
Vadim I. Evlakhov ◽  
Ilya Z. Poyassov ◽  
Tatiana P. Berezina
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Pulmonary Artery Pressure ◽  
Vascular Resistance ◽  
Venous Return ◽  
Filtration Coefficient ◽  
Artery Pressure ◽  
Capillary Filtration ◽  
Capillary Filtration Coefficient ◽  
Pulmonary Microcirculation

Background. The pulmonary arterial and venous vessels are innervated by parasympathetic cholinergic nerves. However, the studies, performed on the isolated rings of pulmonary vessels, can not give answer to the question about the role of cholinergic mechanisms in the changes of pulmonary circulation in full measure. Aim. The comparative analysis of the changes of the pulmonary macro- and microhemodynamics after acetylcholine, atropine, pentamine and nitroglycerine treatment. Materials and methods. The study was carried out on the anesthetized rabbits in the condition of intact circulation with the measurement of the pulmonary artery pressure and flow, venae cavae flows, cardiac output, and also on isolated perfused lungs in situ with stabilized pulmonary flow with measurement of the perfused pulmonary artery pressure, capillary hydrostatic pressure, capillary filtration coefficient and calculation of the pulmonary vascular resistance, pre- and postcapillary resistances. Results. In the conditions of intact circulation after acetylcholine, pentamine and nitroglycerine treatment the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance did not change as a result of decreasing of pulmonary artery flow and left atrial pressure due to diminution of venous return and venae cavaе flows. On perfused isolated lungs acetylcholine caused the increasing of pulmonary artery pressure, capillary hydrostatic pressure, pulmonary vascular resistance, pre- and postcapillary resistance and capillary filtration coefficient. After M-blocker atropine treatment the indicated above parameters of pulmonary microcirculation increased, on the contrary, after N-blocker pentamine treatment they decreased. Nitroglycerine infusion caused less decreasing of the parameters of pulmonary microcirculation in comparison with effects of pentamine, but capillary filtration coefficient decreased to a greater extent. These data indicate that nitroglycerine decreases endothelial permeability of pulmonary microvessels. Conclusion. After activation or blockade of cholinergic mechanisms in the condition of intact circulation the calculated parameter of pulmonary vascular resistance is depended from the ratio of the pulmonary artery pressure and flow and left atrial pressure, which are determined by the venous return. The different character of the changes of pulmonary microcirculatory parameters after M-blocker atropine and N-blocker pentamine treatment is evidence of reciprocal relations of M- and N-cholinoceptors in the nervous regulation of the pulmonary microcirculatory bed.

Pressure-induced smooth muscle cell depolarization in pulmonary arteries from control and chronically hypoxic rats does not cause myogenic vasoconstriction

2005 ◽  
Vol 98 (3) ◽  
pp. 1119-1124 ◽  
Author(s):  
Jay S. Naik ◽  
Scott Earley ◽  
Thomas C. Resta ◽  
Benjimen R. Walker
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Cell Membrane ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arteries ◽  
Barometric Pressure ◽  
Cell Membrane Potential ◽  
Intraluminal Pressure ◽  
Dose Dependent

Chronic obstructive pulmonary diseases, as well as prolonged residence at high altitude, can result in generalized airway hypoxia, eliciting an increase in pulmonary vascular resistance. We hypothesized that a portion of the elevated pulmonary vascular resistance following chronic hypoxia (CH) is due to the development of myogenic tone. Isolated, pressurized small pulmonary arteries from control (barometric pressure ≅ 630 Torr) and CH (4 wk, barometric pressure = 380 Torr) rats were loaded with fura 2-AM and perfused with warm (37°C), aerated (21% O2-6% CO2-balance N2) physiological saline solution. Vascular smooth muscle (VSM) intracellular Ca2+ concentration ([Ca2+]i) and diameter responses to increasing intraluminal pressure were determined. Diameter and VSM cell [Ca2+]i responses to KCl were also determined. In a separate set of experiments, VSM cell membrane potential responses to increasing luminal pressure were determined in arteries from control and CH rats. VSM cell membrane potential in arteries from CH animals was depolarized relative to control at each pressure step. VSM cells from both groups exhibited a further depolarization in response to step increases in intraluminal pressure. However, arteries from both control and CH rats distended passively to increasing intraluminal pressure, and VSM cell [Ca2+]i was not affected. KCl elicited a dose-dependent vasoconstriction that was nearly identical between control and CH groups. Whereas KCl administration resulted in a dose-dependent increase in VSM cell [Ca2+]i in arteries taken from control animals, this stimulus elicited only a slight increase in VSM cell [Ca2+]i in arteries from CH animals. We conclude that the pulmonary circulation of the rat does not demonstrate pressure-induced vasoconstriction.

scholarly journals Cinaciguat, a soluble guanylate cyclase activator, causes potent and sustained pulmonary vasodilation in the ovine fetus

2009 ◽  
Vol 297 (2) ◽  
pp. L318-L325 ◽  
Author(s):  
Marc Chester ◽  
Pierre Tourneux ◽  
Greg Seedorf ◽  
Theresa R. Grover ◽  
Jason Gien ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Left Pulmonary Artery ◽  
Flow Transducer ◽  
Pulmonary Vasodilation

Impaired nitric oxide-cGMP signaling contributes to severe pulmonary hypertension after birth, which may in part be due to decreased soluble guanylate cyclase (sGC) activity. Cinaciguat (BAY 58-2667) is a novel sGC activator that causes vasodilation, even in the presence of oxidized heme or heme-free sGC, but its hemodynamic effects have not been studied in the perinatal lung. We performed surgery on eight fetal (126 ± 2 days gestation) lambs (full term = 147 days) and placed catheters in the main pulmonary artery, aorta, and left atrium to measure pressures. An ultrasonic flow transducer was placed on the left pulmonary artery to measure blood flow, and a catheter was placed in the left pulmonary artery for drug infusion. Cinaciguat (0.1–100 μg over 10 min) caused dose-related increases in pulmonary blood flow greater than fourfold above baseline and reduced pulmonary vascular resistance by 80%. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an sGC-oxidizing inhibitor, enhanced cinaciguat-induced pulmonary vasodilation by >120%. The pulmonary vasodilator effect of cinaciguat was prolonged, decreasing pulmonary vascular resistance for >1.5 h after brief infusion. In vitro stimulation of ovine fetal pulmonary artery smooth muscle cells with cinaciguat after ODQ treatment resulted in a 14-fold increase in cGMP compared with non-ODQ-treated cells. We conclude that cinaciguat causes potent and sustained fetal pulmonary vasodilation that is augmented in the presence of oxidized sGC and speculate that cinaciguat may have therapeutic potential for severe neonatal pulmonary hypertension.

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