Pulmonary versus systemic effects of vasodilator drugs: an in vitro study in isolated intrapulmonary and mesenteric arteries of neonatal piglets

Pérez‐Vizcaíno, Francisco; Villamor, Eduardo; Moro, Manuel; Tamargo, Juan

doi:10.1016/s0014-2999(96)00548-1

Cited by 7 publications

(15 citation statements)

References 28 publications

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“…In the present study the relaxations of conduit porcine IPAs to ATP, ADPβS and 2‐meSATP were endothelium‐independent at all ages. The potency of the ATP‐induced relaxation in large conduit IPA from 2 week‐old pigs in this study was similar to the endothelium‐independent relaxation in the smaller IPA from 10–17 day‐old normal piglets reported by other investigators (Perez‐Vizcaino et al ., 1996). ATP and 2‐meSATP were also found to induce an endothelium‐independent relaxation response in adult rabbit main PA and small human IPAs (Liu et al ., 1989a; Qasabian et al ., 1997).…”

Section: Discussionsupporting

confidence: 91%

“…The role of purines in the newborn and transitional circulation is uncertain. ATP relaxes mature isolated intrapulmonary arteries from man and several other species (Greenberg, 1987; Liu et al ., 1989a,1989b; Purkiss et al ., 1994), and it also relaxes the isolated IPA of 10–17 day‐old piglets (Perez‐Vizcaino et al ., 1996). Purines may be important at birth since blood levels of ATP are increased by exposing the foetal lamb to high oxygen levels, and infusion of the di‐sodium salt of ATP into the foetal lamb reduces the pulmonary vascular resistance to a level comparable to that measured after birth (Konduri et al ., 1997).…”

Section: Introductionmentioning

confidence: 99%

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Vasodilatation of intrapulmonary arteries to P2‐receptor nucleotides in normal and pulmonary hypertensive newborn piglets

McMillan

Burnstock

Haworth

1999

British J Pharmacology

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1 The vasodilator responses of isolated intrapulmonary arteries (IPA) to P2-receptor agonists were investigated during adaptation to extrauterine life in the piglet. The e ect of pulmonary hypertension on the normal response was determined after exposing newborn animals to chronic hypobaric hypoxia (51 kPa) for 3 days. 2 Adenosine 5'-triphosphate (ATP), 2-methylthioATP (2-meSATP), adenosine 5-O-(2-thiodiphosphate) (ADPbS) and uridine 5'-triphosphate (UTP) induced a relaxation in normal newborn piglet IPA pre-contracted with prostaglandin F 2a (PGF 2a ). The relaxations were not a ected by removal of the endothelium. The responses to ATP and ADPbS increased signi®cantly with age. 3 The relaxation responses of IPA to ATP, 2-meSATP and ADPbS continued to increase normally after birth in an hypoxic environment. 4 The results of the study show that vasodilatation of porcine intrapulmonary vessels to nucleotides increased during development from foetus to adult; that the vasodilatation to purines was mediated by P2Y-receptors on the vascular smooth muscle rather than on the endothelium; and that the P2Y-receptor mediated relaxation of IPA remained normal in the pulmonary hypertensive neonate.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Vasodilatation of intrapulmonary arteries to P2‐receptor nucleotides in normal and pulmonary hypertensive newborn piglets

McMillan

Burnstock

Haworth

1999

British J Pharmacology

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“…1-2 mm, second order) and RPA (i.d. ≤ 0.5 mm, fifth order) were carefully dissected from surrounding tissue and cut into 2-3 mm wide rings for studies on intact preparations [15]. During manipulation of the arteries, care was taken not to touch their intimal surface to preserve the endothelium layer.…”

Section: Tissue Preparation and Contractile Tension Recordingmentioning

confidence: 99%

“…The organ baths contained Krebs solution maintained at 37°C and continuously bubbled with a 95% O2-5% CO2 mixture as previously described. Tissues were stretched to a predetermined optimal resting tension of 0.5 g for pulmonary rings and 2.0 g for mesenteric rings [15]. The presence of functional endothelium was tested by the assessment of the relaxant response to ACh (10-6 M) in rings pre-contracted with 5HT (10-5 M).…”

Section: Tissue Preparation and Contractile Tension Recordingmentioning

confidence: 99%

“…This mixture allowed us to avoid possible vasoactive response differences among arteries depending on the vasoconstrictor used [15], and mimics several forms of PH including PE, achieving a high vascular tone that presumably reflects what happens in massive PE [17]. Once equilibration (about 25 min), a concentration-response curve to levosimendan (10-9 M to 3´10-5 M) was carried out by cumulative addition of drug after a steadystate relaxant response was reached after each increment.…”

Section: Experimental Protocolmentioning

confidence: 99%

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Preferential Vasodilator Effects of Levosimendan in Resistance Pulmonary Arteries in a Rodent Pulmonary Embolism Model

Bedo

Grignola

2017

ICFJ

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IntroductionThe pulmonary vasculature consists of large, elastic, extraparenchymal conduit pulmonary arteries (CPA, order 1 to 2) that arise from the sixth aortic arch and small, muscular resistance intrapulmonary arteries (RPA, ≥ 4th order), that originate from the mesenchymal lung bud by capillary plexus expansion [1]. This subdivision is associated with different response to several stimuli. While CPA dilates or fails to constrict to hypoxia, RPA is responsible for hypoxic pulmonary vasoconstriction, control the regional distribution of blood flow and largely determine pulmonary vascular resistance. This functional difference mainly depends on the distribution of electrophysiologically distinct myocytes in CPAs and RPAs arteries [1,2].Levosimendan is a positive inotropic agent (by increasing the sensitivity of troponin C to calcium) with vasodilating properties (by lowering of intracellular free Ca++, opening of different potassium channels and the inhibition of phosphodiesterase type III), also termed inodilator [3,4]. There are several animals studies in different acute pulmonary hypertension (PH) models secondary to thromboxane A2 infusion [5], endotoxemia [6], acute pulmonary embolism (PE) [7,8], and hypoxia [9] and some clinical studies that demonstrated the vasodilator effect of levosimendan on the pulmonary circulation, restoring right ventricular-arterial coupling as it increased right ventricular contractility concomitantly [10,11]. Acute PE-induced PH results from two main mechanisms: HighlightsBackground

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Pulmonary endothelial dysfunction after cardiopulmonary bypass in neonatal pigs

Glavind‐Kristensen¹,

Christensen

Toennesen

et al. 2002

Acta Anaesthesiol Scand

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Pulmonary versus systemic effects of vasodilator drugs: an in vitro study in isolated intrapulmonary and mesenteric arteries of neonatal piglets

Cited by 7 publications

References 28 publications

Vasodilatation of intrapulmonary arteries to P2‐receptor nucleotides in normal and pulmonary hypertensive newborn piglets

Vasodilatation of intrapulmonary arteries to P2‐receptor nucleotides in normal and pulmonary hypertensive newborn piglets

Preferential Vasodilator Effects of Levosimendan in Resistance Pulmonary Arteries in a Rodent Pulmonary Embolism Model

Pulmonary endothelial dysfunction after cardiopulmonary bypass in neonatal pigs

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