Effect of carvedilol and losartan on renal responses to ANG II and adrenergic agonists in fructose-fed rat

Effect of carvedilol and losartan was assessed on insulin sensitivity (IS) and renal responses to angiotensin II (Ang II) and adrenergic agonists in high fructose-fed model of metabolic syndrome in Sprague-Dawley rat. Rats were fed with 20% fructose in drinking water (FR) for 8 weeks. FR received either carvedilol (FRC) or losartan (FRL) at (10mg/kg/day po) for 3 weeks starting from week 5 of the experiment. At the end of treatment, an intravenous insulin glucose tolerance test and the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II were determined. FR exhibited mild hyperglycemia, glucose intolerance and hypertension. In FR, the low IS, as assessed by glucose disappearance rate was restored to that of controls by carvedilol or losartan. The renal responses (%) to NA, PE, ME and Ang II were lower in FR compared to control (control vs FR, 21±5 vs 15±1; 42±6 vs 24±3; 32±7 vs 9±1; 20±5 vs 16±2) respectively. In FR, carvedilol or losartan treatment blunted responses to Ang II to 10±1% and 6±1% respectively. FRC had higher constrictor responses to ME compared to FR (19±3 vs 9±1%). Data demonstrated that Ang II plays an important role in regulating renal haemodynamics in FR and, indicated an interaction between Ang II and adrenergic neurotransmission in these rats. Moreover, carvedilol or losartan treatment improved IS in FR.