Effects of long-term oral treatment with selective vasopressin V2 receptor antagonist (OPC-31260) on adriamycin-induced heart failure in rats

Takeuchi, Masayuki; Lee, Jong–Dae; Shimizu, Hiromasa; Ueda, Takanori

doi:10.1016/j.ijcard.2005.05.009

Cited by 3 publications

(4 citation statements)

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“…Similar results have been reported using another vasopressin V 2 -antagonist, OPC-31260, in normal and CHF dogs [28]. Moreover, long-term OPC-31260 administration did not aggravate cardiac remodeling, cardiac function, or survival, despite significantly increasing the plasma AVP concentration in rat models of postinfarction-induced [29] and adriamycin-induced [30] CHF. Therefore, a compensatory increase in plasma AVP by the V 2 -antagonist may not adversely affect cardiac or renal function during short-or long-term treatment in patients with CHF.…”

Section: Effects Of Tolvaptan On Systemic and Renal Hemodynamicssupporting

confidence: 86%

Effects of Tolvaptan on Systemic and Renal Hemodynamic Function in Dogs with Congestive Heart Failure

Onogawa

Sakamoto

Nakamura

et al. 2011

Cardiovasc Drugs Ther

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Purpose We investigated the effects of tolvaptan, a vasopressin V 2 -receptor antagonist, on diuretic response and systemic and renal hemodynamic characteristics in conscious dogs with congestive heart failure (CHF). We also compared these effects with those of furosemide, a loop diuretic. Methods CHF was induced by rapid right-ventricular pacing at 260 beats/min for at least 3 weeks, and maintained with a pacing rate of 220-240 beats/min. CHF dogs were orally given tolvaptan (10 mg/kg), furosemide (10 mg/kg) and vehicle in random order during the stable CHF state. Urine excretion, systemic and renal hemodynamic parameters, and plasma hormone levels were measured over 6-hour periods after drug administration. Results Tolvaptan induced aquaresis with an increase in free water clearance, resulting in a significant increase in serum sodium concentrations and a decrease in cumulative water balance. Tolvaptan also decreased pulmonary capillary wedge pressure without affecting systemic vascular resistance, glomerular filtration rate or renal blood flow. Tolvaptan tended to increase plasma arginine vasopressin concentrations but did not affect plasma renin activity. In contrast, furosemide induced clear saluresis with increased electrolyte excretion, resulting in decreased pulmonary capillary wedge pressure. However, furosemide also decreased serum potassium concentration and increased plasma arginine vasopressin concentrations and plasma renin activity.Conclusion Tolvaptan elicited a potent aquaretic response and reduced the cardiac preload without unfavorable effects on systemic or renal hemodynamics, the renin-angiotensinaldosterone system, or the sympathetic nervous system in CHF dogs. Thus, tolvaptan may offer a novel approach to remove excess water congestion from patients with CHF.

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Section: Effects Of Tolvaptan On Systemic and Renal Hemodynamicssupporting

confidence: 86%

Effects of Tolvaptan on Systemic and Renal Hemodynamic Function in Dogs with Congestive Heart Failure

Onogawa

Sakamoto

Nakamura

et al. 2011

Cardiovasc Drugs Ther

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“…The chronic side effects are represented by the development of cardiomyopathy and ultimately, irreversible congestive heart failure [1,2] . Great effort has been expended in preventing or mitigating the cardiotoxic side effects of ADR [3][4][5][6][7] ; however, the mechanisms underlying ADR-induced heart failure are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, effects mediated by AT 2 R include inhibition of cell growth, neuronal regeneration, cellular differentiation and possibly vasodilatation [9] . Angiotensin-(1-7) [Ang- (1)(2)(3)(4)(5)(6)(7)] is a peptide formed from either Ang I or Ang II [9] . Ang-(1-7) is considered to be an important peptide fragment of the RAS, and it plays crucial roles that are often opposite from those of Ang II [11] .…”

Section: Introductionmentioning

confidence: 99%

Regulation of angiotensin-(1–7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure

et al. 2011

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Aim:To investigate the possible effects of telmisartan and losartan on cardiac function in adriamycin (ADR)-induced heart failure in rats, and to explore the changes in plasma level of angiotensin-(1-7)[Ang-(1-7)] and myocardial expression of angiotensin II type 1/2 receptors (AT 1 R / AT 2 R) and Mas receptor caused by the two drugs. Methods: Male Sprague-Dawley rats were randomly divided into 4 groups: the control group, ADR-treated heart failure group (ADR-HF), telmisartan plus ADR-treated group (Tel+ADR) and losartan plus ADR-treated group (Los+ADR). ADR was administrated (2.5 mg/kg, ip, 6 times in 2 weeks). The rats in the Tel+ADR and Los+ADR groups were treated orally with telmisartan (10 mg/kg daily po) and losartan (30 mg/kg daily), respectively, for 6 weeks. The plasma level of Ang-(1-7) was determined using ELISA. The mRNA and protein expression of myocardial Mas receptor, AT 1 R and AT 2 R were measured using RT-PCR and Western blotting, respectively. Results: ADR significantly reduced the plasma level of Ang-(1-7) and the expression of myocardial Mas receptor and myocardial AT 2 R, while significantly increased the expression of myocardial AT 1 R. Treatment with telmisartan and losartan effectively increased the plasma level of Ang-(1-7) and suppressed myocardial AT 1 R expression, but did not influence the expression of Mas receptor and AT 2 R. Conclusion: The protective effects of telmisartan and losartan in ADR-induced heart failure may be partially due to regulation of circulating Ang-(1-7) and myocardial AT 1 R expression.Keywords: angiotensin-(1-7); Mas; angiotensin I receptor; angiotensin II receptor; adriamycin; heart failure; telmisartan; losartan Acta Pharmacologica Sinica (2011Sinica ( ) 32: 1345Sinica ( -1350 doi: 10.1038/aps.2011 published online 3 Oct 2011 Original Article # The first two authors contributed equally to this work. * To whom correspondence should be addressed. npg an oncogene as well as a receptor for Ang-(1-7) [13] . In a previous work, Mas receptor-deficient mice showed higher blood pressure values, impaired endothelial function, decreased NO production and lower endothelial NO synthetase expression [14] , indicating that the Ang-(1-7)/Mas receptor axis plays an important role in cardioprotective and antihypertensive effects. Importantly, Ang-(1-7) can prevent heart failure after myocardial ischemia [15] . Some recent studies have reported that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two classes of drugs that target RAS, may prevent ADR-induced cardiotoxicity [16][17][18][19] . However, the underlying mechanisms are largely unclear. In the present study, we investigated the regulation of two ARBs (telmisartan and losartan) on plasma Ang-(1-7) levels and the mRNA and protein expression of the myocardial AT 1 R, AT 2 R and Mas receptors in ADR-induced heart failure. Materials and methods Animals Experimental protocolRats were randomly divided into four groups: (1) the control group (n=10, intraperitoneally injected an...

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“…In rats treated with this molecule, no significant increase in mortality was found after 6 weeks' treatment, with respect to controls notwithstanding the high levels of circulating vasopressin achieved [21]. This study was the first to focus less on the efficacy of pharmacological action of aquaretics in a particular clinic-experimental model, and more on an equally important collateral aspect in this pathological condition: elevated levels of vasopressin.…”

Section: Aquaretics In Heart Failurementioning

confidence: 82%

Aquaretic Agents: Whats Beyond the Treatment of Hyponatremia?

Bolignano

Coppolino²,

Criseo³

et al. 2007

CPD

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Unlike the more commonly used diuretics, aquaretic agents can induce an increase in urinary volume without incurring a loss of electrolytes. These molecules belong to a family of vasopressin receptor antagonists, V2 in particular, that regulate optional renal water re-absorption via the synthesis and expression of aquaporin-2. In view of their properties, they have become the agent of choice in the treatment of hyponatremic states with water retention, and different studies have demonstrated that they are more effective and practical to use than other traditional approaches in the treatment of diseases such as cirrhosis-related ascites, SIADH and, above all, heart failure. However, the future probably holds the promise of new and unexpected applications for this type of drug in the treatment of several conditions, including polycystic kidney and glomerular disease, glaucoma and Meniere's syndrome.

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Effects of long-term oral treatment with selective vasopressin V2 receptor antagonist (OPC-31260) on adriamycin-induced heart failure in rats

Cited by 3 publications

References 26 publications

Effects of Tolvaptan on Systemic and Renal Hemodynamic Function in Dogs with Congestive Heart Failure

Effects of Tolvaptan on Systemic and Renal Hemodynamic Function in Dogs with Congestive Heart Failure

Regulation of angiotensin-(1–7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure

Aquaretic Agents: Whats Beyond the Treatment of Hyponatremia?

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