No abstract

The cardioprotective effects of resveratrol are well established in animal models of metabolic disease but are yet to be investigated in a combined model of hypertension and diabetes. This study investigated the ability of resveratrol's antioxidant and anti-inflammatory effects to prevent cardiovascular complications in the spontaneously hypertensive streptozotocin-induced diabetic rat. Diabetes was induced in eight-week-old male spontaneously hypertensive rats via a single intravenous injection of streptozotocin. Following this, resveratrol was administered orally for an eight-week period until the animals were sixteen weeks of age. Upon completion of the treatment regime assessments of oxidative stress, lipid peroxidation, inflammation, and cardiovascular function were made. Resveratrol administration to hypertensive-diabetic animals did not impact upon blood glucose or haemodynamics but significantly reduced oxidative stress, lipid peroxidation, and inflammatory cytokines. Reductions in systemic levels of oxidative stress and inflammation conferred improvements in vascular reactivity and left ventricular pump function and electrophysiology. This study demonstrates that resveratrol administration to hypertensive diabetic animals can elicit cardioprotective properties via antioxidant and anti-inflammatory effects. The observed preservation of cardiovascular function was independent of changes in blood glucose concentration and haemodynamics, suggesting that oxidative stress and inflammation are key components within the pathological cascade associated with hypertension and diabetes.

1 Release of acetylcholine from parasympathetic nerves is inhibited by neuronal M 2 muscarinic receptors. The e ects of streptozotocin-induced diabetes on prejunctional M 2 and postjunctional M 3 muscarinic receptor function in rat trachea and ileum were investigated in vitro. 2 Neuronal M 2 muscarinic receptor function was tested by measuring the ability of an agonist, pilocarpine, to inhibit and an antagonist, methoctramine, to potentiate electrical ®eld stimulation (EFS)-induced contraction of trachea and ileum. Concentration-response curves to pilocarpine and methoctramine were shifted to the left in both to a greater degree in diabetics than controls. 3 In trachea, post-junctional M 3 muscarinic receptor function was increased since maximum contractile responses to the muscarinic agonists acetylcholine and carbachol were greater in diabetics than controls. This increase o set the increased function of the inhibitory neuronal M 2 muscarinic receptors since EFS-induced, frequency-dependent contraction was equal in control and diabetic rats. 4 In contrast, post-junctional M 3 muscarinic receptor function was unchanged by diabetes since concentration-response curves to acetylcholine and carbachol were not di erent between groups. Thus, EFS-induced contractions of the ileum were decreased in diabetics versus controls. 5 In conclusion, inhibitory M 2 muscarinic receptors on parasympathetic nerves in the trachea and ileum are hyperfunctional in diabetic rats. The function of post-junctional M 3 muscarinic receptors in the trachea, but not the ileum, is also increased in diabetes. 6 The dysfunction of inhibitory, neuronal M 2 muscarinic receptors in the airways may protect against hyperreactivity and in the ileum may contribute to gastrointestinal dysmotility associated with diabetes.