Key result
In a rat model of diabetic cardiopathy, adverse effects of high-dose rosiglitazone (30mg/kg), including weight gain and left ventricular hypertrophy, were reversed by adding amiloride (2mg/kg).
Why the study?
Does rosiglitazone alone or in combination with amiloride improve outcomes in a rat model of diabetic cardiopathy?
Does rosiglitazone alone or in combination with amiloride improve outcomes in a rat model of diabetic cardiopathy?
The combination of rosiglitazone and amiloride reverses the adverse cardiovascular effects of high-dose rosiglitazone in a murine model of diabetic cardiopathy.
Answers are grounded in this paper and cite their sources.
No change to rosiglitazone use; leaves open whether amiloride mitigates its effects in human diabetic cardiopathy.
AIMS: Rosiglitazone (RSZ), a PPARγ agonist was potent efficacious insulin sensitizing blockbuster drug for treatment of Type 2 diabetes mellitus (T2DM) but the benefit of PPARγ activation in congestive heart failure (CHF) was controversial. The present work was planned to study the role of RSZ in diabetic cardiopathy. MAIN METHODS: Zucker fa/fa rats, the genetic model of T2DM were subjected to constriction of suprarenal abdominal aorta so that they represent a combined model of diabetes and cardiopathy. The development cardiopathy was assessed biochemically (plasma BNP and aldosterone levels), using echocardiography and expression angiotensin II receptor type 1a gene in heart and Endothelin-1 gene in aorta. Rats were treated with RSZ and in combination with amiloride for four weeks and were assessed to evaluate the effect of RSZ or amiloride or its combination on antidiabetic activity, adverse or toxic effects and congestive heart failure status. KEY FINDINGS: RSZ shows its anti-diabetic effect from 0.3mg/kg dose onwards and at 3mg/kg dose levels it caused beneficial effects (reduction of blood pressure) on cardiovascular system and at highest (30mg/kg) dose it starts showing adverse effects like body weight gain, edema, left ventricular hypertrophy. However, when highest dose of RSZ animals were treated with amiloride (ENaC inhibitor) at 2mg/kg the reversal of the adverse effects was evident, indicating the combination of RSZ and amiloride is beneficial in diabetic cardiopathy model. SIGNIFICANCE: RSZ and amiloride combination appeared promising treatment in diabetic patients with cardiopathy without any side effect.
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Giri et al. (2016) studied Diabetic cardiopathy. Rosiglitazone and amiloride was evaluated on Antidiabetic activity, adverse or toxic effects, and congestive heart failure status. In a rat model of diabetic cardiopathy, adverse effects of high-dose rosiglitazone (30mg/kg), including weight gain and left ventricular hypertrophy, were reversed by adding amiloride (2mg/kg).
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