methylatropine and Body-Weight

The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

Topics: Animals; Antihypertensive Agents; Atropine Derivatives; Autonomic Nervous System; Body Weight; Bradycardia; Female; Hemodynamics; Hypertension; Menopause; Ovariectomy; Parasympatholytics; Physical Conditioning, Animal; Propranolol; Rats, Inbred SHR; Rats, Wistar; Reproducibility of Results; Resistance Training; Time Factors

In this study we assessed the role of Bezold-Jarisch reflex (BJR) in the regulation of blood pressure (BP) of malnourished (MN) and control rats (CN) with sino-aortic denervation (SAD). Fischer rats were fed diets containing either 6% (MN) or 15% (CN) protein for 35 days after weaning. These rats underwent sham or SAD and catheterization of femoral artery and vein for BP measurements and drug injection. Phenylbiguanide (PBG 5 μg/kg, i.v.) for activation BJR, produced bradycardia (-317±22 bpm for CN vs. -372±16 bpm for MN) and hypotension (-57±4 mm Hg for CN vs. -54±6 mm Hg for MN. After SAD, MN rats had reduced hypotensive (-37±7 mm Hg for MN vs. -82±6 mm Hg for CN) and bradycardic (-124±17 for MN vs. -414±20 bpm CN) responses to BJR activation. To evaluate the contribution of the parasympathetic component due to BJR for the fall in BP, methyl atropine bromide, was given between two injections of PBG (5 μg/kg) separated by 10 min each other. Both bradycardic (-216±21 bpm before and -4±3 bpm after for CN -226±43 bpm before and -9±20 bpm after for MN) and hypotensive (-42±4 mm Hg before and -6±1 mm Hg after for CN -33±9 mm Hg before and -5±2 mm Hg after for MN) responses were abolished in CN and MN groups. These data indicate that dietary protein malnutrition changes the relation between baroreflex and BJR required for maintenance of the BP during malnourishment.

Topics: Animals; Atropine Derivatives; Biguanides; Blood Pressure; Body Weight; Denervation; Dose-Response Relationship, Drug; Heart Rate; Male; Malnutrition; Muscarinic Antagonists; Nitroprusside; Phenylephrine; Protein-Energy Malnutrition; Rats; Rats, Inbred F344; Reflex; Serotonin Receptor Agonists; Sinoatrial Node; Vasoconstrictor Agents; Vasodilator Agents

We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m(3) sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.

Topics: Acetylcholinesterase; Administration, Intranasal; Alkaline Phosphatase; Animals; Atropine Derivatives; Body Weight; Bronchoalveolar Lavage Fluid; Butyrylcholinesterase; Cell Count; Chemical Warfare Agents; Dose-Response Relationship, Drug; Guinea Pigs; Heart Rate; Inhalation Exposure; Instillation, Drug; Lung; Male; Organ Size; Oxygen; Parasympatholytics; Pulmonary Edema; Pulmonary Surfactants; Sarin; Time Factors

To determine the time-dependent effects of rosiglitazone (RSG) on blood pressure (MAP) and baroreflex sensitivity (BRS) and the involvement of nitric oxide (NO) in these effects.. Male Sprague-Dawley rats were treated with RSG (8 mg/kg per day, orally) or saline for 4, 8 and 12 weeks. BRS was determined by linear regression method with bolus injections of phenylephrine (PE-BRS) or sodium nitroprusside (NP-BRS). Insulin sensitivity (M value) was determined by euglycemic hyperinsulinemic clamp study. Vascular and cardiac responsiveness to isoproterenol, acetylcholine and NP were determined after ganglionic blockade. Effects of endogenous NO were examined by Nomega-nitro-L-arginine-methyl ester (L-NAME) administration.. RSG treatment time-dependently decreased circulating lipids, insulin, glucose levels and insulin resistance (HOMA-IR) but increased plasma NOx levels. M values were progressively decreased in control rats, but remained unchanged in RSG-treated rats. Chronic RSG treatment progressively lowered MAP but reciprocally increased heart rate (HR). In addition, chronic RSG treatment significantly attenuated HR changes to methylatropine but enhanced HR changes to propranolol. Twelve-week RSG treatment enhanced PE-BRS which was suppressed by methylatropine but not propranolol, and attenuated NP-BRS which was sustained after methylatropine or propranolol. Moreover, 12-week RSG treatment also diminished cardiac responsiveness to isoproterenol and augmented vascular responsiveness to acetylcholine, but not to NP. L-NAME eliminated the differences in MAP and HR between groups, and reversed both RSG-induced enhanced PE-BRS and attenuated NP-BRS. Plasma NOx levels were highly correlated with RSG-mediated changes in the baseline MAP, HR and BRS.. These data suggest that RSG-induced NO production is important for the time-dependent effects of RSG on MAP and BRS in rats.

Topics: Administration, Oral; Animals; Arteries; Atropine Derivatives; Autonomic Nervous System; Baroreflex; Blood Glucose; Blood Pressure; Body Weight; Heart Rate; Insulin; Insulin Resistance; Linear Models; Lipids; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Propranolol; Rats; Rats, Sprague-Dawley; Rosiglitazone; Sensitivity and Specificity; Thiazolidinediones; Time Factors

To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m(3) of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

Topics: Acetylcysteine; Acute Disease; Animals; Atropine Derivatives; Body Weight; Bronchoalveolar Lavage Fluid; Chemical Warfare Agents; Guinea Pigs; Inhalation Exposure; Lung Diseases; Male; Organ Size; Organothiophosphorus Compounds; Proteins; Pulmonary Surfactants; Respiratory Mucosa

Earlier studies from the authors' laboratory showed that malnourishment induces alterations in the cardiovascular homeostasis increasing the basal mean arterial pressure and heart rate. In this study, the authors evaluated whether the sympathetic and parasympathetic efferent activities contribute to changes in the cardiovascular homeostasis through altered modulation of the arterial baroreflex of malnourished rats. After weaning, male Fischer rats were given 15% (Normal Protein--NP) or 6% (Low Protein--LP) protein diet for 35 d. The baroreflex gain and latency were evaluated before and after selective autonomic blockades in control and malnourished rats. It was observed that malnourishment affected the baroreflex gain in response to activation and deactivation of the arterial baroreflex. Moreover, malnourished rats showed increased baroreflex latency as compared to that of control rats. Regarding the autonomic efferent activity directed to the heart, the data showed increased sympathetic and decreased parasympathetic efferent activities in malnourished rats, and such alterations could be related to the observed changes in the arterial baroreflex gain as well as in the basal mean arterial pressure and heart rate.

Topics: Animals; Arteries; Atropine Derivatives; Baroreflex; Body Weight; Cardiovascular Diseases; Gene Expression Regulation; Male; Metoprolol; Pressure; Proteins; Rats; Rats, Inbred F344

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of heart rate were measured in conscious, unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk). Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine, respectively. Autonomic control of heart rate and intrinsic heart rate were determined by use of methylatropine and propranolol. Resting bradycardia was observed in trained mice compared with sedentary animals [485 +/- 9 vs. 612 +/- 5 beats/min (bpm)], whereas mean arterial pressure was not different between the groups (106 +/- 2 vs. 108 +/- 3 mmHg). Baroreflex-mediated tachycardia was significantly enhanced in the trained group (6.97 +/- 0.97 vs. 1.6 +/- 0.21 bpm/mmHg, trained vs. sedentary), whereas baroreflex-mediated bradycardia was not altered by training. The tachycardia induced by methylatropine was significantly increased in trained animals (139 +/- 12 vs. 40 +/- 9 bpm, trained vs. sedentary), whereas the propranolol effect was significantly reduced in the trained group (49 +/- 11 vs. 97 +/- 11 bpm, trained vs. sedentary). Intrinsic heart rate was similar between groups. In conclusion, dynamic exercise training in mice induced a resting bradycardia and an improvement in baroreflex-mediated tachycardia. These changes are likely related to an increased vagal and decreased sympathetic tone, similar to the exercise response observed in humans.

Topics: Animals; Atropine Derivatives; Autonomic Nervous System; Blood Pressure; Body Weight; Cardiovascular System; Heart Rate; Male; Mice; Mice, Inbred C57BL; Physical Conditioning, Animal; Pressoreceptors; Propranolol; Restraint, Physical

Adult Flinders-Sensitive Line (FSL) rats are significantly more sensitive to the behavioral and physiologic effects of muscarinic agonists than are control, Flinders-Resistant Line (FRL) rats; therefore, they resemble humans with depressive disorders. The present study examined the sensitivity of prepubertal and pubertal FSL and FRL rats to the hypothermic and locomotor inhibitory effects of the muscarinic agonist, oxotremorine, and compared these findings to the regional development of muscarinic receptor binding in similarly aged rats. The FSL rats were significantly more sensitive (-1.85 degrees +/- 0.2 degrees C) than the FRL rats (-0.65 degrees +/- 0.15 degrees C) to the hypothermic effect of 0.25 mumol/kg of oxotremorine at the earliest age tested (18 days postpartum) and became progressively more sensitive throughout the period of testing (FSL -2.8 degrees +/- 0.24 degrees C versus FRL -0.5 degrees +/- 0.16 degrees C at 61 days postpartum, data represent the mean +/- SEM of pooled male and female). Significant increases in muscarinic receptor number in FSL rat brain were observed only in older (61 days postpartum) rats. These results are consistent with the suggestion that the FSL rat is a genetic animal model of depression, but also indicate that the differences in muscarinic sensitivity cannot be accounted for exclusively by differences in the number, per se, of muscarinic receptors.

Topics: Aging; Animals; Atropine Derivatives; Body Temperature; Body Weight; Brain; Depression; Disease Models, Animal; Female; Locomotion; Male; Oxotremorine; Quinuclidinyl Benzilate; Radioligand Assay; Rats; Receptors, Muscarinic

The effects of continuous infusion of cholinergic drugs on behavior in normal rats and on impaired acquisition and retention of several behavioral tasks in rats with basal forebrain (BF) lesions were investigated. Physostigmine and oxotremorine were infused continuously with a miniosmotic pump for 3 weeks, and the performance on several different behavioral tasks was examined during the infusion. In normal rats high doses of physostigmine (4 and 8 mg/kg/day s.c.) produced significant changes in general behavior and impaired performance in the Morris water maze. Oxotremorine (0.25-2 mg/kg/day s.c.) had no significant effects on general behavior or cognitive performance in normal rats, although severe cataracts developed at the high dose (4 mg/kg/day). A deficit in motor habituation in rats with BF lesions produced by bilateral injections of ibotenic acid (30 nmol on each side) was improved markedly by the chronic administration of physostigmine (2 mg/kg/day) and oxotremorine (1 mg/kg/day). BF lesions produced severe impairments in acquisition and retention in a passive avoidance task, an active avoidance and the Morris water maze, which was characterized by a marked disruption of retention. The impairment was also ameliorated markedly by the cholinergic drugs, whereas other behavioral impairments were not affected by the drugs. These results indicate that the continuous administration of cholinergic drugs produces a marked improvement of acquisition and retention in rats with BF lesions, and suggest that the impairment in cognitive performance, especially with regard to retention, caused by BF lesions is due to the disruption of the BF-cortical cholinergic pathway.

Topics: Acetylcholinesterase; Animals; Atropine Derivatives; Avoidance Learning; Basal Ganglia; Body Weight; Male; Memory; Motor Activity; Parasympathomimetics; Physostigmine; Rats; Rats, Inbred Strains; Reaction Time; Substantia Innominata

The ontogeny of functional sympathetic neural, adrenal medullary, and extra-adrenal components of adrenergic control of heart rate was compared in neonatal Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Borderline hypertensive (BHR) rats using combined sequential pharmacological blockade and surgical intervention. Baseline heart rate recorded from awake and unrestrained pups was lower in BHR than in WKY or SHR at 5 days of age. Tonic sympathetic neural control of heart rate was inferred from bradycardia after treatment with the adrenergic neuron-blocking agent, bretylium tosylate. Bradycardia after bretylium treatment was observed at 2, 5 and 8 days of age in all strains, suggesting tonic sympathetic neural control of heart rate during the first postnatal week. Parasympathetic control of heart rate was inferred from heart rate increase after treatment with the muscarinic receptor blocker, atropine methyl nitrate, in pups pretreated with bretylium. Tachycardia following atropine methyl nitrate was substantial in all 24-day-old pups. Control of heart rate by neurally mediated release of catecholamines from the adrenal medulla was inferred from bradycardia following administration of the ganglionic blocking agent, hexamethonium, to pups pretreated with bretylium and atropine methyl nitrate. Heart rate decreases after hexamethonium were found in 2-day-old WKY and BHR pups, and at 5 and 8 days in all strains. Adrenalectomy was performed in additional animals to confirm the adrenal catecholamine influence on heart rate. The influence of residual circulating catecholamines on neonatal heart rate was inferred from bradycardia following administration of the beta-adrenergic receptor blocking agent, atenolol, in pups pretreated with bretylium, methylatropine, and hexamethonium. Bradycardia was observed in pups of each strain and at all ages after atenolol treatment. Strain differences in autonomic controls of heart rate were most pronounced at 24 days of age. At 24 days of age both SHR and BHR pups showed increased adrenal catecholamine and parasympathetic influences on heart rate compared to WKY. Thus, prior to weaning, rats differing in their genetic predisposition to hypertension showed a unique pattern of autonomic control over heart rate which may be related to adult cardiovascular regulation.

Topics: Age Factors; Animals; Animals, Newborn; Antihypertensive Agents; Atenolol; Atropine Derivatives; Autonomic Nervous System; Body Weight; Bretylium Tosylate; Female; Heart Rate; Hexamethonium; Hexamethonium Compounds; Hypertension; Male; Parasympathetic Nervous System; Parasympatholytics; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sympathetic Nervous System

The cholinergic antagonists atropine (ATR) and atropine methylnitrate (ATRMN) were chronically administered to inbred Dahl hypertension-sensitive (S/JR) and -resistant (R/JR) rats maintained on an 8.0% NaCl-containing diet. The effects on blood pressure (BP), heart rate (HR), and mortality were then examined during and after a four week period of treatment. Administration of ATR (7.2 mg/day) or ATRMN (2.4 mg/day) attenuated the development of salt-induced hypertension (HT) in the S/JR strain but had relatively little effect on BP in the R/JR strain. HR during the treatment period was significantly greater in S/JR and R/JR rats that received ATR or ATRMN than vehicle-treated controls. Each drug also reduced HT-related mortality in S/JR rats. In general, the effects of ATR on BP and mortality were greater than those of ATRMN. However, the results suggest that the central and peripheral cholinergic systems participate in the development of salt-induced HT in the S/JR rat.

Topics: Animals; Atropine; Atropine Derivatives; Blood Pressure; Body Weight; Drug Administration Schedule; Heart Rate; Hypertension; Male; Rats; Rats, Inbred Strains; Sodium Chloride; Time Factors