Abstract
This study was conducted to explore the hypothesis that the endogenous superoxide anions (O2−) and nitric oxide (NO) system of the paraventricular nucleus (PVN) regulates the cardiac sympathetic afferent reflex (CSAR) contributing to sympathoexcitation in obese rats induced by a high-fat diet (42% kcal as fat) for 12 weeks. CSAR was evaluated by monitoring the changes of renal sympathetic nerve activity (RSNA) and the mean arterial pressure (MAP) responses to the epicardial application of capsaicin (CAP) in anaesthetized rats. In obese rats with hypertension (OH group) or without hypertension (OB group), the levels of PVN O2−, angiotensinII (Ang II), Ang II type 1 receptor (AT1R), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were elevated, whereas neural NO synthase (nNOS) and NO were significantly reduced. Moreover, CSAR was markedly enhanced, which promoted the elevation of plasma norepinephrine levels. The enhanced CSAR was attenuated by PVN application of the superoxide scavenger polyethylene glycol-superoxide dismutase (PEG-SOD) and the NO donor sodium nitroprusside (SNP), and was strengthened by the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC) and the nNOS inhibitor N(ω)-propyl-l-arginine hydrochloride (PLA); conversely, there was a smaller CSAR response to PLA or SNP in rats that received a low-fat (12% kcal) diet. Furthermore, PVN pretreatment with the AT1R antagonist losartan or with PEG-SOD, but not SNP, abolished Ang II-induced CSAR enhancement. These findings suggest that obesity alters the PVN O2− and NO system that modulates CSAR and promotes sympathoexcitation.
Highlights
The prevalence of obesity is increasing globally, and it is well known that obesity is often associated with hypertension and cardiovascular diseases (CVD)
After 12 weeks of high-fat diet (HFD) consumption, plasma insulin, cholesterol, and triglyceride levels, as well as heart weight, body weight, and white adipose tissue (WAT) mass were increased in obese rats without hypertension (OB) and obese rats with hypertension (OH)
The CAP-induced cardiac sympathetic afferent reflex (CSAR) was much stronger in OH rats compared with OB rats (p < 0.05 for each, Figure 1B), and in OB rats compared with control and OR rats (p < 0.05 for each, Figure 1B)
Summary
The prevalence of obesity is increasing globally, and it is well known that obesity is often associated with hypertension and cardiovascular diseases (CVD). The activation of the sympathetic nervous system plays an important role in the pathogenesis of obesity-related hypertension and CVD [1,2,3,4]. The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site in regulating the autonomic and cardiovascular activities [10,11], and one of the main components of the central neurocircuitry of CSAR [12,13]. The PVN participates in sympathetic overactivation in obesity and obesity-related hypertensive rats [14]. It can be supposed that the PVN is a major site in the regulation of CSAR in obese rats
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