Red wine but not alcohol consumption improves cardiovascular function and oxidative stress of the hypertensive-SHR and diabetic-STZ rats

Abstract

ABSTRACT Hypertension and diabetes development had been characterized as idiopathic disorders tightly interconnected, and therefore it is essential to understand how the functionality of neurohormonal pathways are involved in both diseases. Hypertensive and diabetic patients have shown increased systolic blood pressure (SBP), oxidative stress, vascular hypertrophy, and remodeling. It is well established that the long-term consumption of red wine and/or polyphenol-stilbene causes cardioprotective and antihypertensive effects; however, some functions remain unrevealed. Downstream pathways such as reactive oxygen species (ROS), sympathoadrenal axis represented by β1-adrenoceptors, and renin–angiotensin system via angiotensin-II receptors critically contribute to hypertension development. Aims This raised the issue of whether in vivo long-term red wine treatment can act as a modulator of these targets. Main methods We monitored SBP, glucose tolerance, oxidative stress, and cardiovascular function. Aortic and atrial tissues from normotensive-WKY, hypertensive-SHR, and diabetic-STZ animals, chronically exposed to red wine (3.715 ml/kg/v.o/day) or alcohol (12%) for 21-days, were used to measure contractile/relaxation responses by force transducers. Key findings: red wine, but not alcohol, prevented the increase of SBP and hyperglycemic peak. Additionally, was observed prevention of oxidative stress metabolites formation and an improvement in ROS scavenging antioxidant capacity of SHR. We also revealed that red wine intake enhances the endothelium-dependent relaxation, decreases the hypercontractile mediated by angiotensin-II in the aorta, and via β1-adrenoceptors in the atrium. Significance The long-term consumption of red wine can improve oxidative stress and the functionality of angiotensin-II and β1-adrenoceptors, inspiring new pharmacologic and dietetic therapeutic approaches for the treatment of hypertension and diabetes. Abbreviation Acronyms and/or abbreviations: [Ca2+]cyt = Cytosolic Ca2+ Concentration; ACh = Acetylcholine; ANG II = Angiotensin II; AT1 = ANG II type 1 receptor; AUC = Area Under the Curve; Ca2+ = Calcium; Endo + = Endothelium Intact; Fen = Phenylephrine (1 μM); GTT = Glucose Tolerance Test; ISO = Isoprenaline (isoproterenol); KHN = Krebs-Henseleit Nutrient; LA = Left Atria; LH = Lipid Hydroperoxide; NO = Nitric Oxide; RA = Right Atria; RAS = Renin-Angiotensin System; ROS = Reactive Oxygen Species; SBP = Systolic Blood Pressure; SHR = Spontaneously Hypertensive Rats; STZ = Streptozotocin; WKY = Normotensive Wistar Kyoto Rats.