Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels.

Lataro RM, Silva CA, Fazan R Jr, Rossi MA, Prado CM, Godinho RO, Salgado HC. Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure. Am J Physiol Regul Integr Comp Physiol 305: R908 -R916, 2013. First published August 28, 2013 doi:10.1152/ajpregu.00102.2013.-Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. The parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling, and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4 wk of pyridostigmine administration, per os, methylatropine and propranolol were used to evaluate the cardiac sympathovagal balance. The tachycardic response caused by methylatropine was considered to be the vagal tone, whereas the bradycardic response caused by propranolol was considered to be the sympathetic tone. In conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output, and contractility of the left ventricle. It was demonstrated that the long-term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.

Spectral analysis of heart rate (HR) has been widely used to assess the autonomic cardiovascular control. A nonlinear approach, known as symbolic analysis, has been reported to be very useful to assess the autonomic control of cardiovascular system in humans, but very few studies reported on the differences between these two approaches on experimental models. Two distinct approaches were used to elicit autonomic changes in conscious Wistar rats: (1) pharmacological blockade of cardiac autonomic receptors with atenolol (ATE, N = 9) or methylatropine (ATR, N = 9) and (2) mild changes in arterial pressure (AP) induced by phenylephrine (PHE, N = 9) or sodium nitroprusside (NPS, N = 9). Series of cardiac interval (CI) and systolic AP (SAP) were assessed using spectral analysis and symbolic dynamics. Results show that, for spectral analysis, the power in high frequency band of CI and the power in low frequency band of SAP are the most reliable indices of vagal and sympathetic modulation, respectively. For symbolic analysis, results point 0V% and 1V% to be related to sympathetic and 2UV% to vagal modulation. Interestingly, the incidence of 1V patterns, hitherto with unknown meaning, was revealed the best index of sympathetic modulation in the rat and should be accounted for in the future studies.

-Baroreflex responses to changes in arterial pressure are impaired in spontaneously hypertensive rats (SHR). Mean arterial pressure (MAP), heart rate (HR), and regional vascular resistances were measured before and during electrical stimulation (5-90 Hz) of the left aortic depressor nerve (ADN) in conscious SHR and normotensive control rats (NCR). The protocol was repeated after ␤-adrenergic-receptor blockade with atenolol. SHR exhibited higher basal MAP (150 Ϯ 5 vs. 103 Ϯ 2 mmHg) and HR (393 Ϯ 9 vs. 360 Ϯ 5 beats/min). The frequency-dependent hypotensive response to ADN stimulation was preserved or enhanced in SHR. The greater absolute fall in MAP at higher frequencies (Ϫ68 Ϯ 5 vs. Ϫ38 Ϯ 3 mmHg at 90-Hz stimulation) in SHR was associated with a preferential decrease in hindquarter (Ϫ43 Ϯ 5%) vs. mesenteric (Ϫ27 Ϯ 3%) resistance. In contrast, ADN stimulation decreased hindquarter and mesenteric resistances equivalently in NCR (Ϫ33 Ϯ 7% and Ϫ30 Ϯ 7%). Reflex bradycardia was also preserved in SHR, although its mechanism differed. Atenolol attenuated the bradycardia in SHR (Ϫ88 Ϯ 14 vs. Ϫ129 Ϯ 18 beats/min at 90-Hz stimulation) but did not alter the bradycardia in NCR (Ϫ116 Ϯ 16 vs. Ϫ133 Ϯ 13 beats/min). The residual bradycardia under atenolol (parasympathetic component) was reduced in SHR. MAP and HR responses to ADN stimulation were also preserved or enhanced in SHR vs. NCR after deafferentation of carotid sinuses and contralateral right ADN. The results demonstrate distinct differences in central baroreflex control in conscious SHR vs. NCR. Inhibition of cardiac sympathetic tone maintains reflex bradycardia during ADN stimulation in SHR despite impaired parasympathetic activation, and depressor responses to ADN stimulation are equivalent or even greater in SHR due to augmented hindquarter vasodilation. spontaneously hypertensive rats; arterial pressure; heart rate; atenolol BARORECEPTOR AFFERENT SENSITIVITY (1, 2, 19, 43) and baroreflex-mediated changes in heart rate (HR) (25, 38) are consistently impaired in spontaneously hypertensive rats (SHR). More controversial is baroreflex control of sympathetic nerve activity, which has been reported to be impaired (8, 10), preserved (22,33,46), or augmented (46) in SHR. The inconsistent findings may reflect, in part, differential baroreflex control of sympathetic activity to different regions and use of anesthesia in many of the studies. In the majority of studies, baroreflex responses were measured in response to drug-induced changes in arterial blood pressure (BP), which does not allow assessment of reflex changes in vascular resistance.The goal of the present study was to compare the magnitude of reflex responses to electrical stimulation of baroreceptor afferents in the aortic depressor nerve (ADN) in conscious normotensive control rats (NCR) and SHR. This approach allowed us to assess not only the fall in HR but also the decrease in BP and regional vascular resistances. Furthermore, we hypothesized that electrical activation of baroreceptor afferents would more eff...

Analysis of heart rate variability (HRV) by nonlinear approaches has been gaining interest due to their ability to extract additional information from heart rate (HR) dynamics that are not detectable by traditional approaches. Nevertheless, the physiological interpretation of nonlinear approaches remains unclear. Therefore, we propose long-term (60 min) protocols involving selective blockade of cardiac autonomic receptors to investigate the contribution of sympathetic and parasympathetic function upon nonlinear dynamics of HRV. Conscious male Wistar rats had their electrocardiogram (ECG) recorded under three distinct conditions: basal, selective (atenolol or atropine), or combined (atenolol plus atropine) pharmacological blockade of autonomic muscarinic or β-adrenergic receptors. Time series of RR interval were assessed by multiscale entropy (MSE) and detrended fluctuation analysis (DFA). Entropy over short (1 to 5, MSE) and long (6 to 30, MSE) time scales was computed, as well as DFA scaling exponents at short (α, 5 ≤ ≤ 15), mid (α, 30 ≤ ≤ 200), and long (α, 200 ≤ ≤ 1,700) window sizes. The results show that MSE is reduced under atropine blockade and MSE is reduced under atropine, atenolol, or combined blockade. In addition, while atropine expressed its maximal effect at scale six, the effect of atenolol on MSE increased with scale. For DFA, α decreased during atenolol blockade, while the α increased under atropine blockade. Double blockade decreased α and increased α Results with surrogate data show that the dynamics during combined blockade is not random. In summary, sympathetic and vagal control differently affect entropy (MSE) and fractal properties (DFA) of HRV. These findings are important to guide future studies. Although multiscale entropy (MSE) and detrended fluctuation analysis (DFA) are recognizably useful prognostic/diagnostic methods, their physiological interpretation remains unclear. The present study clarifies the effect of the cardiac autonomic control on MSE and DFA, assessed during long periods (1 h). These findings are important to help the interpretation of future studies.