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

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.

KEYWORDS:

• Hypertension
• diabetes
• red wine
• alcohol
• functional food
• neurotransmission

Credit authorship contribution statement

Participated in research design: Bomfim, G.H.S., Musial, D.C., Rocha, K., Jurkiewicz, A., Jurkiewicz, N.H. Conducted experiments: Bomfim, G.H.S., Musial, D.C., Rocha, K. Contributed new reagents or analytic tools: Jurkiewicz, A., Jurkiewicz, N.H. Performed data analysis: Bomfim, G.H.S., Musial, D.C., Rocha, K. Wrote or contributed to the writing of the manuscript: Bomfim, G.H.S., Musial, D.C., Rocha, K., Jurkiewicz, N.H.

Acknowledgments

We would like to thank the Instituto Nacional de Farmacologia (INFAR), Brazil for the continued support. Also, the Professor Elizabeth Micai for the extensive and detailed review of the manuscript English grammar. This work was supported by the Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES [BEX 8477/13-2]; the Fundação de Amparo a Pesquisa do Estado de São Paulo [FAPESP: 2014/01569-0].

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Highlights

• Red wine, but not alcohol, prevented blood pressure increase and hyperglycemic peak;

• Red wine improves ROS scavenging antioxidant capacity in hypertensive-SHR rats;

• Endothelium-dependent relaxation was enhanced in hypertensive-SHR and diabetic-STZ rats;

• Hypercontractile via angiotensin-II and β₁-adrenoceptors was reduced in SHR and STZ rats;

• Long-term consumption of red wine can improve the aortic and atrial functionality;

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.