Inotropic effects of angiotensin II on human cardiac muscle in vitro.

Moravec, Christine S.; Schluchter, Mark D.; Paranandi, Lata; Czerska, Barbara; Stewart, Robert W.; Rosenkranz, Eliot R.; Bond, Meredith

doi:10.1161/01.cir.82.6.1973

Cited by 117 publications

(60 citation statements)

References 54 publications

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“…As clearly shown in the results, L-158,809 potently suppressed the angiotensin II-induced vasopressor response, with a potency similar to those reported previously (7). We also confirmed the angiotensin II-induced negative inotropic effect in this study, although the substance has been reported to exert positive (8), no (9), negative (10), or biphasic inotropic effects (11). L-158,809 attenuated the angiotensin II-induced negative inotropic response in a dose-related manner, which has not been reported elsewhere.…”

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confidence: 90%

Cardiovascular Effects of L-158,809, a New Angiotensin Type 1 Receptor Antagonist, Assessed Using the Halothane-Anesthetized In Vivo Canine Model

Yoneyama

Sugiyama

Yoshida

et al. 2002

Japanese Journal of Pharmacology

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ABSTRACT-L-158,809 is a new angiotensin II type 1 receptor antagonist. We simultaneously assessed its antagonistic potency and cardiovascular effects with the halothane-anesthetized in vivo canine model (n = 5). L-158,809 was intravenously infused over 10 min at escalating doses of 0.03, 0.3 and 3 mg /kg. Angiotensin II (0.1 mg/kg, i.v.)-induced vasopressor and negative inotropic responses were significantly suppressed from the low dose L-158,809. Meanwhile, L-158,809 did not affect any of the cardiovascular parameters except that QTc was slightly shortened after the high dose administration. These results support the previous in vitro knowledge that L-158,809 is a highly selective angiotensin II receptor antagonist.Keywords: L-158,809, Angiotensin II, QT interval L-158,809 is a highly selective angiotensin II type 1 (AT 1 ) receptor antagonist whose affinity for AT 1 receptor has been shown to be greater than the existing angiotensin II receptor antagonists (1). Indeed, the affinity of L-158,809 for AT1 receptors is similar to that of angiotensin II itself (1). Moreover, a recent experimental study (2) has shown that L-158,809 attenuates early left ventricular remodeling during canine myocardial infarction. However, information is still limited regarding the relationship between the doses of L-158,809 that block angiotensin II receptor and those that affect the cardiovascular variables. In this study, we simultaneously assessed the in vivo angiotensin II receptor blocking action and cardiovascular effects of L-158,809, using the halothane-anesthetized, closedchest canine model (3 -5).All experiments were performed according to Guidelines for Animal Experiments, Yamanashi Medical University. Experiments were carried out using beagle dogs weighing approximately 10 kg. The animals had been fed with about 240 g /day of standard dog foods (CD-55a; CLEA Japan, Tokyo) containing 0.41 g /100 g of NaCl for >1 month in the Animal Laboratory for Research of Yamanashi Medical University. Dogs were anesthetized initially with thiopental sodium (30 mg /kg, i.v.). After intubation, 1.0% halothane vaporized with 100% oxygen was inhaled with a ventilator (SN-480-3; Shinano, Tokyo). Tidal volume and respiratory rate were set at 20 ml /kg and 15 strokes /min, respectively. To prevent blood clotting, heparin calcium (100 IU /kg) was intravenously administered.The surface lead II ECG was obtained from the limb electrodes. Corrected QT interval (QTc) was obtained using Bazett's formula (6). The systemic blood pressure was measured at the left femoral artery. A thermodilution catheter (TC-704; Nihon Kohden, Tokyo) was positioned at the right side of the heart through the right femoral vein. The cardiac output was measured by a standard thermodilution method using a cardiac output computer (MFC-1100, Nihon Kohden). The total peripheral vascular resistance (TPR) was calculated using the following basic equation: TPR = mean blood pressure / cardiac output. A quad-polar electrodes catheter was positioned at the non-coronary cusp of the a...

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supporting

confidence: 90%

Cardiovascular Effects of L-158,809, a New Angiotensin Type 1 Receptor Antagonist, Assessed Using the Halothane-Anesthetized In Vivo Canine Model

Yoneyama

Sugiyama

Yoshida

et al. 2002

Japanese Journal of Pharmacology

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“…Several previous studies have shown that PoAT correlates closely with mean pulmonary arterial pressure and pulmonary vascular resistance [13][14][15] be supported by in vitro data showing that angiotensin II produces positive inotropic effects in the isolated heart [19,20]. Since angiotensin II also produces right ventricular preload reduction by venodilatation [12], the net effect on PoAcc is probably a summation of responses.…”

Section: Discussionmentioning

confidence: 81%

Comparative effects of angiotensin II on Doppler parameters of left and right heart systolic and diastolic blood flow.

Lipworth

Dagg

1994

Brit J Clinical Pharma

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“…Angiotensin II (AII) elicits a positive inotropic effect (PIE) in the cardiac muscles of certain mammalian species that include man (Moravec et al, 1990) and the rabbit (Dempsey et al, 1971;Freer et al, 1976;Ishihata & Endoh, 1993). Direct activation of specific receptors by AII is considered to trigger a signal-transduction process that results in the PIE (Dempsey et al, 1971;Freer et al, 1976;Kobayashi et al, 1978;Moravec et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Species‐related differences in inotropic effects of angiotensin II in mammalian ventricular muscle: receptors, subtypes and phosphoinositide hydrolysis

Ishihata

Endoh

1995

British J Pharmacology

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1 Experiments were carried out to clarify the mechanisms responsible for variations in the positive inotropic effect (PIE) of angiotensin II (All) on ventricular muscles from various mammals. We examined the density of AII receptors, the relative proportions of receptor subtypes and the acceleration of the hydrolysis of phosphoinositide that was induced by AII, as well as the PIE of AII in ventricular muscles from the rabbit, dog, rat and ferret. having high affinity for the receptors, and indicating that AT, and AT2 subtypes were present in equal numbers. In the other species the AT, subtype of receptors was predominant. 5 In all four species AII caused a concentration-dependent acceleration of the hydrolysis of phosphoinositide in ventricular slices that had been prelabelled with myo-[3H]-inositol. 6 The results indicate that the signal-transduction process distal to acceleration of the hydrolysis of phosphoinositide may be responsible for the wide range of species variations in the inotropic action of AII on mammalian ventricular myocardium.

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Inotropic effects of angiotensin II on human cardiac muscle in vitro.

Cited by 117 publications

References 54 publications

Cardiovascular Effects of L-158,809, a New Angiotensin Type 1 Receptor Antagonist, Assessed Using the Halothane-Anesthetized In Vivo Canine Model

Cardiovascular Effects of L-158,809, a New Angiotensin Type 1 Receptor Antagonist, Assessed Using the Halothane-Anesthetized In Vivo Canine Model

Comparative effects of angiotensin II on Doppler parameters of left and right heart systolic and diastolic blood flow.

Species‐related differences in inotropic effects of angiotensin II in mammalian ventricular muscle: receptors, subtypes and phosphoinositide hydrolysis

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