Endothelin receptor blockade attenuates air embolization-induced pulmonary hypertension in sheep

Miyahara, Takashige; Koizumi, Tomonobu; Kubo, Keishi; Hanaoka, Masayuki; Kaneki, Toshimichi; Yamamoto, H.; Ge, Ri-Li; Kobayashi, Toshio; Shibamoto, Toshishige

doi:10.1016/s0014-2999(99)00732-3

Cited by 6 publications

(13 citation statements)

References 27 publications

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“…The pleiotropic actions of ETs make this family of mediators potential key players in several cardiovascular disorders, including PE. The modulation of the ETs that we observed in our rat model of APAE are consistent with those reported in other models of PE [9][10][11][12][13][14][15].…”

Section: Discussionsupporting

confidence: 92%

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Effects of a selective endothelin A receptor antagonist, ABT-627, in healthy normotensive anaesthetized rats developing acute pulmonary air embolism

et al. 2002

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Acute pulmonary air embolism (APAE) injures the vascular endothelium in the lung and results in pulmonary hypertension (PH). Endothelins (ETs), a family of potent vasoactive peptides, are known to be associated with PH of various aetiologies. We evaluated the effects of ABT-627, a selective ET(A) receptor (ET(A)-R) antagonist in a rat model of APAE over 3 h. APAE rats developed a higher right ventricular systolic pressure (RVSP), lower mean arterial blood pressure (MABP), and had lower PaO(2). At 3 h, arterial plasma levels of ET-1 were increased. ABT-627-treated controls showed no effects. However, ABT-627 significantly lowered RVSP during APAE, abolished the short recovery phase (within 10-25 min) of MABP without affecting the subsequent lowering of MABP, and improved oxygen saturation in APAE rats. These results show that ET(A)-R subtype is involved in the pathogenesis of APAE since a blockade of this receptor subtype attenuated the cardiopulmonary deterioration and improved blood gas exchanges in rats with this disease.

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Section: Discussionsupporting

confidence: 92%

“…Other studies have demonstrated abnormalities of the ET system in patients with PE [8]. Additional non-clinical studies assessing the implication of the ETs in rabbit, canine and porcine models of PE using either selective or non-selective ET-R antagonists [9][10][11][12][13][14][15] have provided further support.…”

Section: Introductionmentioning

confidence: 91%

Effects of a selective endothelin A receptor antagonist, ABT-627, in healthy normotensive anaesthetized rats developing acute pulmonary air embolism

et al. 2002

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“…Synthesis of the peptide and expression of ET A R also increase in response to hypertensive stimuli (Ivy et al, 1998;Black et al, 2000;Chen and Oparil, 2000). ET-1 antagonists, on the other hand, may reverse pulmonary hypertension of various etiologies in both newborn and adult animals (Di Carlo et al, 1995;Miyahara et al, 1999;Jasmin et al, 2001). In the neonate in particular, ET-1 antagonists are effective against the hypertension resulting from hypoxia (lamb and piglet) (Wang et al, 1995;Perrault et al, 2001), experimental diaphragmatic hernia (lamb) (Thébaud et al, 2000), and increased blood flow (lamb) (Petrossian et al, 1999) and against the rebound hypertension consequent to abrupt discontinuation of NO inhalation (lamb) (McMullan et al, 2001).…”

mentioning

confidence: 99%

The Endothelin A Receptor Antagonists PD 156707 (CI-1020) and PD 180988 (CI-1034) Reverse the Hypoxic Pulmonary Vasoconstriction in the Perinatal Lamb

Coe

Haleen²,

Welch³

et al. 2002

J Pharmacol Exp Ther

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Endothelin-1 (ET-1) is considered an intermediary in the constrictor response of the pulmonary vasculature to hypoxia and, by extension, is assigned a prime role in the pathogenesis of pulmonary hypertension. We report here the antihypertensive action in the conscious newborn lamb of two novel endothelin A receptor antagonists, sodium 2-benzo-[1,3]dioxol-5-yl-4-(4-methoxy-phenyl)-4-oxo-3-(3,4,5-trimethoxy-benzyl)-but-2-enoate (PD 156707) and 4-( ,2]thiazine-3-carboxylic acid potassium (PD 180988), differing in chemical properties and half-life within the body. PD 156707 and PD 180988, given in the right atrium as a bolus followed by infusion, had little or no effect on pulmonary and systemic hemodynamics under normoxia. Conversely, they both reversed the pulmonary hypertension due to alveolar hypoxia while producing minor changes, or no change at all, in systemic vascular resistance. Furthermore, their pulmonary vascular effect outlasted administration. Pulmonary hypertension being elicited by infusion of the thromboxane A 2 analog, 9,11-epithio-11,12-methano-thromboxane A 2 (ONO-11113) was instead not amenable to ET A R inhibition. Blood levels of ET-1, which rose with hypoxia but not ONO-11113 treatment, were not changed by either antagonist. Consistent with findings in vivo, when using isolated pulmonary resistance arteries from term fetal lamb, PD 156707 curtailed the hypoxia-but not the ONO-11113-induced constriction. We conclude that PD 156707 and PD 180988 are selective inhibitors of pulmonary vasoconstriction resulting from hypoxia. Our findings support the use of these or allied compounds in the management of pulmonary hypertension in the neonate.

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“…In porcine hypoxic pulmonary hypertension, endothelin contributes to pulmonary vasoconstriction through ET A -receptor stimulation. 138 ET-1 levels are increased in air embolisation-induced pulmonary hypertension in sheep 139 and hypoxiareoxygenation-induced pulmonary hypertension in piglets, 106 which suggests that ET-1 is involved in the pathogenesis of these forms of pulmonary hypertension. In monocrotaline-induced pulmonary hypertension in rats, the ET A antagonist, TA-0201, is as effective as an oral prostacyclin analogue in the prevention of progression of pulmonary hypertension and right ventricular hypertrophy.…”

Section: Anti-endothelin Agents and Pulmonary Hypertensionmentioning

confidence: 99%

Role of endothelin in cardiovascular disease

Agapitov

Haynes

2002

J Renin Angiotensin Aldosterone Syst

154

119

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Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system.

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Endothelin receptor blockade attenuates air embolization-induced pulmonary hypertension in sheep

Cited by 6 publications

References 27 publications

Effects of a selective endothelin A receptor antagonist, ABT-627, in healthy normotensive anaesthetized rats developing acute pulmonary air embolism

Effects of a selective endothelin A receptor antagonist, ABT-627, in healthy normotensive anaesthetized rats developing acute pulmonary air embolism

The Endothelin A Receptor Antagonists PD 156707 (CI-1020) and PD 180988 (CI-1034) Reverse the Hypoxic Pulmonary Vasoconstriction in the Perinatal Lamb

Role of endothelin in cardiovascular disease

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