Circulating angiotensin II deteriorates left ventricular function with sympathoexcitation via brain angiotensin II receptor

Abstract

Sympathoexcitation contributes to the progression of heart failure. Activation of brain angiotensin II type 1 receptors (AT1R) causes central sympathoexcitation. Thus, we assessed the hypothesis that the increase in circulating angiotensin II comparable to that reported in heart failure model affects cardiac function through the central sympathoexcitation via activating AT1R in the brain. In Sprague-Dawley rats, the subcutaneous infusion of angiotensin II for 14 days increased the circulating angiotensin II level comparable to that reported in heart failure model rats after myocardial infarction. In comparison with the control, angiotensin II infusion increased 24 hours urinary norepinephrine excretion, and systolic blood pressure. Angiotensin II infusion hypertrophied left ventricular (LV) without changing chamber dimensions while increased end-diastolic pressure. The LV pressure–volume relationship indicated that angiotensin II did not impact on the end-systolic elastance, whereas significantly increased end-diastolic elastance. Chronic intracerebroventricular infusion of AT1R blocker, losartan, attenuated these angiotensin II-induced changes. In conclusion, circulating angiotensin II in heart failure is capable of inducing sympathoexcitation via in part AT1R in the brain, subsequently leading to LV diastolic dysfunction.

Up‐regulation of hypothalamic arginine vasopressin by peripherally administered furosemide in transgenic rats expressing arginine vasopressin‐enhanced green fluorescent protein

“…However, attention should be paid to the interaction between the sympathetic nervous system and the RAAS. Previous reports have revealed that circulating angiotensin II activated the sympathetic nervous system in part via brain angiotensin I type I receptors . We could not directly modulate the sympathetic nervous system and/or RAAS in the present study.…”

Central Inhibition of Tumor Necrosis Factor Alpha Reduces Hypertension by Attenuating Oxidative Stress in the Rostral Ventrolateral Medulla in Renovascular Hypertensive Rats

“…The sympatho-excitatory responses triggered by RAAS activation are mainly caused by the Ang-II through AT1 receptors in both periphery and central nervous system (CNS) (Braga et al, 2011). In the CNS, Ang-II effects involve the activation of AT1 receptors in the subfornical organ (SFO), with recruitment of the enzyme NADPH oxidase and ROS formation, especially superoxide anion (O 2 •– ), in the SFO, PVN, and RVLM (Griendling et al, 1994; Zimmerman et al, 2004; Braga et al, 2011; Shinohara et al, 2015). In addition to the already mentioned effects, Ang-II may also act as growth factor and as a stimulating agent of proinflammatory cytokines such as IL-6 and TNF-α (Kalra et al, 2002).…”

Disruption of Central Antioxidant Property of Nuclear Factor Erythroid 2-Related Factor 2 Worsens Circulatory Homeostasis with Baroreflex Dysfunction in Heart Failure

“…We have demonstrated that central AT 1 R-induced oxidative stress causes sympathoexcitation in hypertension and heart failure. Moreover, baroreflex is found to have failed in hypertension and heart failure [ 5 , 6 , 7 , 17 , 18 ]. However, it has not been fully clarified whether the central AT 1 R-induced oxidative stress impaired baroreflex function or not.…”

“…The sympathetic nerve activities were presented as the normalized unit of the low frequency component (0.04–0.60 Hz) of the systolic arterial pressure variability [ 6 , 7 ]. Baroreflex sensitivity was measured using the spontaneous sequence method, as in our previous study [ 6 , 7 , 17 , 18 , 22 ].…”