Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

Intragastric gavage with denatonium benzoate acutely induces neuronal activation in the solitary tract nucleus via the vagal afferent pathway

Natural toxic substances have a bitter taste and their ingestion sends signals to the brain leading to aversive oral sensations. In the present study, we investigated chronological changes in c-Fos immunoreactivity in the nucleus tractus solitarius (NTS) to study the bitter taste reaction time of neurons in the NTS. Equal volumes (0.5 mL) of denatonium benzoate (DB), a bitter tastant, or its vehicle (distilled water) were administered to rats intragastrically. The rats were sacrificed at 0, 0.5, 1, 2, 4, 8, or 16 h after treatment. In the vehicle-treated group, the number of c-Fos-positive nuclei started to increase 0.5 h after treatment and peaked 2 h after gavage. In contrast, the number of c-Fos-positive nuclei in the DB-treated group significantly increased 1 h after gavage. Thereafter, the number of c-Fos immunoreactive nuclei decreased over time. The number of c-Fos immunoreactive nuclei in the NTS was also increased in a dose-dependent manner 1 h after gavage. Subdiaphragmatic vagotomy significantly decreased DB-induced neuronal activation in the NTS. These results suggest that intragastric DB increases neuronal c-Fos expression in the NTS 1 h after gavage and this effect is mediated by vagal afferent fibers.

Central 5-HT2A receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats

Activation of 5-hydroxytryptamine (5-HT) 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.

Ovariectomy does not affect the cardiac sympathovagal balance of female SHR but estradiol does

The low incidence of cardiovascular diseases, including hypertension, in premenopausal women has led to the conclusion that ovarian hormones may have a protective effect on the cardiovascular system. We evaluated the effects of ovariectomy and/or estradiol on sympathovagal balance and heart rate variability (HRV) in female spontaneously hypertensive rats (SHR) with tachycardia and compared them to Wistar rats (12 weeks old; N = 8-12). Ovariectomy (OVX) and/or estradiol (10 µg/kg) did not affect basal arterial pressure in either rat strain, but estradiol increased basal heart rate (HR) in OVX SHR (454 ± 18 vs 377 ± 9 bpm). HR changes elicited by methylatropine and propranolol were used to evaluate the sympathovagal balance. Ovariectomy did not affect the cardiac sympathovagal balance of any group, while estradiol increased sympathetic tone in OVX SHR (120 ± 8 vs 56 ± 10 bpm) and sham-operated Wistar rats (57 ± 7 vs 28 ± 4 bpm), and decreased the parasympathetic tone only in OVX SHR (26 ± 7 vs 37 ± 5 bpm). HRV was studied in the frequency domain (Fast Fourier Transformation). Spectra of HR series were examined at low frequency (LF: 0.2-0.75 Hz) and high frequency (HF: 0.75-3 Hz) bands. The power of LF, as well as the LF/HF ratio, was not affected by ovariectomy, but estradiol increased both LF (29 ± 4 vs 18 ± 3 nu in Wistar sham-operated, 26 ± 5 vs 15 ± 3 nu in Wistar OVX, 50 ± 3 vs 38 ± 4 nu in SHR sham-operated, and 51 ± 3 vs 42 ± 3 nu in SHR OVX) and LF/HF (0.48 ± 0.08 vs 0.23 ± 0.03 nu in Wistar sham-operated, 0.41 ± 0.14 vs 0.19 ± 0.05 nu in Wistar OVX, 0.98 ± 0.11 vs 0.63 ± 0.11 nu in SHR sham-operated, and 1.10 ± 0.11 vs 0.78 ± 0.1 nu in SHR OVX). Thus, we suggest that ovariectomy did not affect the cardiac sympathovagal balance of SHR or Wistar rats, while estradiol increased the sympathetic modulation of HR.

Effect of 4-aminoantipyrine on gastric compliance and liquid emptying in rats

Dipyrone (Dp) delays gastric emptying (GE) in rats. There is no information about whether 4-aminoantipyrine (AA), one of its metabolites, has the same effect. The objectives of the present study were to assess the effects of AA and Dp on GE when administered intravenously (iv) and intracerebroventricularly (icv) (240 æmol/kg and 4 æmol/animal, respectively) and on gastric compliance when administered iv (240 æmol/kg). GE was determined in male Wistar rats weighing 250-300 g (5-10 per group) after icv or iv injection of the drug by measuring percent gastric retention (GR) of a saline meal labeled with phenol red 10 min after administration by gavage. Gastric compliance was estimated in anesthetized rats (10-11 per group), with the construction of volume-pressure curves during intragastric infusion of a saline meal. Compliance was significantly greater in animals receiving Dp (mean ± SEM = 0.26 ± 0.009 mL/mmHg) and AA (0.24 ± 0.012 mL/mmHg) than in controls (0.19 ± 0.009 mL/mmHg). AA and Dp administered iv significantly increased GR (64.4 ± 2.5 and 54.3 ± 3.8 percent, respectively) compared to control (34 ± 2.2 percent), a phenomenon observed only with Dp after icv administration. Subdiaphragmatic vagotomy reduced the effect of AA (GR = 31.4 ± 1.5 percent) compared to sham-treated animals. Baclofen, a GABA B receptor agonist, administered icv significantly reduced the effect of AA (GR = 28.1 ± 1.3 percent). We conclude that Dp and AA increased gastric compliance and AA delayed GE, with the participation of the vagus nerve, through a pathway that does not involve a direct action of the drug on the central nervous system.

Effect of antipyrine on the gastric emptying of liquid in rats

Antipyrine (At) and dipyrone (Dp) delay gastric emptying (GE) in rats. The objective of the present study was to assess the effects of intravenous (iv) and intracerebroventricular (icv) administration of At and Dp on the GE of liquid by rats. GE was assessed in male Wistar rats (5-10 in each group) 10 min after the icv or iv drug injection by measuring percent gastric retention ( percentGR) of a saline test meal labeled with phenol red 10 min after administration by gavage. The At iv group was significantly higher (64.4 ± 2.6 percent) compared to control (33.4 ± 1.5 percent) but did not differ from the Dp group (54.3 ± 3.8 percent). After icv administration of At, percentGR (34.2 ± 2 percent) did not differ from control (32.6 ± 1.9 percent), but was significantly higher after Dp (54.5 ± 2.3 percent). Subdiaphragmatic vagotomy significantly reduced percentGR in the At group (30.2 ± 0.7 percent) compared to the sham group, but was significantly higher than in the controls (23.0 ± 0.5 percent). In the animals treated with At iv, baclofen significantly reduced percentGR (28.3 ± 2.4 percent) compared to vehicle-treated animals (55.2 ± 3.2 percent). The same occurred in the animals treated iv with vehicle and icv with baclofen. Although vagotomy and baclofen reduced percentGR per se, the reduction was twice more marked in the animals treated with At. The results suggest that At administered iv, but not icv, delays GE of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABA B receptors in the central nervous system.

Brainstem origin of duodenal vagal preganglionic parasympathetic neurons. A WGA-HRP study in the ferret (Mustela Putorius Furo), a human model

The projections of vagal brainstem neurons to the duodenal segment of the gastrointestinal tract were studied in the ferret using the WGA-HRP neurohistochemical technique. Fourteen adult ferrets with weights ranging from 800 gm to 1500 gm were used for the study. The muscular wall of the duodenum of six ferrets was injected with 0.1 ml of 5 WGA-HRP in 0.5 M sodium chloride. The eight remaining ferrets were used as controls. Two of these had injections of 0.1 ml normal saline into the muscular wall of the duodenum. The second set of two ferrets was injected with 0.1 ml of 5 WGA-HRP in buffer after bilateral truncal vagotomy. The third set of two ferrets received intraperitoneal injection of 0.1 ml of 5 WGA-HRP while, in the last set, the tracer was injected into the hepatic portal vein. Following the injections, the ferrets were allowed to survive for 48-72 hours after which each ferret was perfused transcardially first with normal saline followed by a fixative containing 1 paraformaldehyde and 1.25 glutaraldehyde in 0.1 M phosphate buffer, pH 7.4 at room temperature and finally with 10 buffered sucrose at 4 degrees C. Transverse serial frozen sections of the brainstem were then taken and processed for WGA-HRP neurohistochemistry and were analyzed under light and dark-field illuminations. The analyses of the sections taken from the six ferrets injected with WGA-HRP revealed neurons labelled with the tracer in the dorsal motor nucleus of the vagus nerve (DMNV). Sections taken from the control ferrets did not reveal any WGA-HRP labelled neurons in the brainstem

Vagal and sympathetic control of heart rate during exercise by sedentary and exercise-trained rats

1. The present investigation was undertaken to study the vagal and sympathetic effects of an acute bout of exercise on ten sedentary (S) and nine trained (T) rats. The exercise training was performed 5 times a week for 13 weeks on a motor treadmill, at 1.0 mph, 15% grade for 60 min. 2. Heart rate (HR) was recorded at rest and during exercise, 15% grade at 0.5, 0.8 and 1.0 mph, for 3 min per stage. Vagal and sympathetic effects were studied after the administration of methylatropine (3 mg/kg) and propranolol (4 mg/kg). 3. Exercise training significantly attenuated cardiac acceleration at 0.8 (441 +/- 8 vs 486 +/- 9 bpm in S, P < 0.05) and 1.0 mph (466 +/- 12 vs 508 +/- 6 bpm in S, P < 0.05). The vagal effect was significantly increased in the T group at 0.8 (72 +/- 5 vs 32 +/- 10 bpm in S, P < 0.05) and 1.0 mph (46 +/- 8 vs 15 +/- 7 bpm in S, P < 0.05). The sympathetic effect was significantly decreased in the T group at 0.8 (73 +/- 9 vs 112 +/- 9 bpm in S, P < 0.05) and 1.0 mph (96 +/- 11 vs 125 +/- 7 bpm in S, P < 0.05). The intrinsic HR behavior was not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)