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Arterial baroreceptors can be divided into two categories dependent on whether their axons are myelinated (A-fiber) or unmyelinated (C-fiber). We investigated the effect of periaxonal resiniferatoxin (RTX), a blocker of C-fiber baroreceptor activity, on the open-loop static characteristics of the arterial baroreflex. The baroreceptor region of the right aortic depressor nerve was isolated, and intra-baroreceptor region pressure (BRP) was changed from 60 to 180 mm Hg in 10 anesthetized Sprague–Dawley rats. Open-loop static characteristics of the neural arc from BRP to efferent sympathetic nerve activity (SNA), peripheral arc from SNA to arterial pressure (AP), and total reflex arc from BRP to AP were estimated. Although blocking C-fiber activity with RTX resulted in a lower response range (33.7 ± 4.6% and 49.4 ± 4.8%, P < 0.01) and higher minimum SNA (78.0 ± 4.7% and 53.6 ± 5.0%, P < 0.001) of the steady-state neural arc, the peak SNA response to BRP was greater at a BRP of 160 mm Hg (− 37.87 ± 5.83% and − 26.28 ± 4.90%, P = 0.01). RTX also resulted in a lower response range (27.8 ± 5.0 mm Hg and 40.9 ± 5.2 mm Hg, P < 0.01) and higher minimum AP (92.4 ± 4.7 mm Hg and 79.1 ± 4.9 mm Hg, P < 0.001) of the total reflex arc. Despite these changes, the maximum slope of the neural arc and the maximum gain of the total reflex arc did not differ significantly after RTX. These data suggest that A-fiber baroreceptors can regulate AP and maintain the maximum gain when systemic AP is around the normal operating range. In contrast, C-fiber baroreceptors are critically important for reductions in SNA and AP when systemic AP is raised above the normal operating range. [ABSTRACT FROM AUTHOR]

Abstract: The participation of acetylcholine-activated potassium current (I K,ACh) and hyperpolarization-activated pacemaker current (I f) in vagal bradycardia were examined using vagally-innervated preparations of guinea-pig atria. Preparations were maintained in Krebs–Henseleit solution (36 °C). Before treatment, trains of vagal stimuli (10 s at 2, 5 and 10 Hz) produced graded bradycardias displaying rapid onset and offset. Tertiapin-Q (300 nM), which blocks I K,ACh, had no effect on baseline atrial rate. In tertiapin-Q, vagal bradycardia displayed a gradual onset and offset, with a peak response ~50% of that recorded in control conditions. Cumulative addition of 1 mM ZD7288 (blocker of I f) caused atrial rate to fall by ~60%, but had no further effect on the amplitude of the vagal bradycardia, while response onset and offset became slightly faster. From these observations, we argue that (i) vagal bradycardia was attributable primarily to activation of I K,ACh, (ii) vagal modulation of I f had a minor influence on the rate of onset and offset of bradycardia, and (iii) removal of the influence of I K,ACh unmasked a slow response, of undetermined origin, to vagal stimulation. In a separate set of experiments we compared the effects of 1 mM Ba2+ and 300 nM tertiapin-Q on vagal bradycardia. Ba2+ reduced baseline atrial rate and the response to vagal stimulation. Subsequent cumulative addition of tertiapin-Q had no additional effect on baseline atrial rate, but caused further reduction in the amplitude of vagal bradycardia, suggesting that 1 mM Ba2+ did not achieve a complete block of I K,ACh in this preparation. [Copyright &y& Elsevier]

An α 2A -adrenergic agonist guanfacine improves autonomic imbalance in attention-deficit hyperactivity disorder, suggesting that it may be useful to correct autonomic imbalance in chronic heart failure (CHF) patients. To investigate the effects of guanfacine on cardiac autonomic nerve activities, a microdialysis technique was applied to anesthetized rabbit heart. Acetylcholine (ACh) and norepinephrine (NE) concentrations in atrial dialysates were measured as indices of cardiac autonomic nerve activities. Guanfacine at a dose of 100 μg/kg significantly decreased heart rate and increased dialysate ACh concentration without decreasing sympathetic NE release. Guanfacine may be useful for vagal activation therapy in CHF patients. [ABSTRACT FROM AUTHOR]

Arterial pressure (AP) elevates as a logarithmic function of exogenously administered dose of norepinephrine (NE). In contrast, AP is nearly linearly correlated with efferent sympathetic nerve activity (SNA) during acute baroreflex intervention. The present study aimed at quantifying the relationship between SNA and plasma NE concentration during acute baroreflex intervention. Carotid sinus regions were isolated from systemic circulation in five Wistar Kyoto rats, and carotid sinus pressure was changed among 60, 100, 120, 140, and 180 mm Hg every 2 min. Arterial blood (0.2 ml) was obtained at each pressure level for plasma NE measurement. Maximum AP and minimum AP were 153.34 ± 6.28 and 67.31 ± 4.92 mm Hg, respectively, in response to pressure perturbation. Plasma NE correlated linearly with SNA for individual animal data (slope: 0.957 ± 0.090 pg·ml − 1 ·% − 1 , intercept: 46.57 ± 7.22 pg/ml, r 2 : ranged from 0.923 to 0.992) and also for group averaged data (NE = 0.956 × SNA + 47.97, r 2 = 0.982). Blockade of neuronal NE uptake by intravenous desipramine (1 mg/kg) administration increased the slope (2.966 ± 0.686 pg·ml − 1 ·% − 1 , P < 0.05) and the intercept (168.73 ± 28.53 pg/ml, P < 0.01) of the plasma NE–SNA relationship. These results indicate that the relationship between SNA and plasma NE concentration was nearly linear within the normal physiological range of acute baroreflex control of AP. While plasma NE concentration can reflect changes in SNA, it may also overestimate the sympathetic outflow from the central nervous system when neuronal NE uptake is impaired systemically. [ABSTRACT FROM AUTHOR]