Apocynin reduces blood pressure and restores the proper function of vascular endothelium in SHR

• Published in: Vascular pharmacology 2016-12, Vol.87, p.38-48
• Main Authors: Perassa, Ligia A, Graton, Murilo E, Potje, Simone R, Troiano, Jéssica A, Lima, Mariana S, Vale, Gabriel T, Pereira, Ariana A.F, Nakamune, Ana Claúdia M.S, Sumida, Doris H, Tirapelli, Carlos R, Bendhack, Lusiane M, Antoniali, Cristina
• Format: Article
• Language: English
• Subjects: Acetophenones - pharmacology; Acetylcholine; Acetylcholine - pharmacology; Animals; Aorta; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Apocynin; Arteries; Bioavailability; Blood pressure; Blood Pressure - drug effects; Calcium; Calcium - metabolism; Cardiovascular; CYBB protein; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial dysfunction; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; eNOS; Hypertension - drug therapy; Hypertension - physiopathology; Male; Muscles; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitroprusside - pharmacology; NOX4 protein; Oxidative stress; Oxidative Stress - drug effects; Phenylephrine; Phenylephrine - pharmacology; Rats; Rats, Inbred SHR; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - metabolism; SHR; Smooth muscle; Sodium; Sodium nitroprusside; Vascular endothelial growth factor
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2016.06.005

Abstract This study has evaluated how the vascular endothelium of hypertensive rats chronically treated with apocynin affects acetylcholine (ACh), sodium nitroprusside (SNP), and phenylephrine (PE) action on the NO signal transduction pathway in endothelial (EC) and vascular smooth muscle cells. Treatment with apocynin significantly reduced the mean arterial pressure in spontaneously hypertensive rats (SHR). In addition, apocynin improved the impaired ACh hypotensive effect on SHR. Although systemic oxidative stress was high in SHR, SHR treated with apocynin and normotensive rats presented similar systemic oxidative stress levels. Endothelium significantly blunted PE contractions in intact aortas of treated SHR. The ACh effect was impaired in resistance arteries and aortas of SHR, but this same effect was improved in treated SHR. The SNP potency was higher in intact resistance arteries of treated SHR than in intact resistance arteries of untreated SHR. NO and calcium concentrations increased, whereas reactive oxygen species levels decreased in EC of treated SHR. Aortas of untreated and treated SHR did not differ in terms of sGC alpha or beta units expression. Aorta of treated SHR expressed higher eNOS levels as compared to aorta of untreated SHR. The study groups did not differ with respect to NOX1, NOXO1, or NOX4 expression. However, treatment with apocynin normalized overexpression of NOX2 and its subunit p47phox in aortas of SHR. Based on all the results presented in this study, we suggest apocynin increases NO biovailability by different mechanisms, restoring the proper function of vascular endothelium in SHR.