methylatropine and Tachycardia

The crosstalk between the immune and the autonomic nervous system may impact the cardiovascular function. Toll-like receptors are components of the innate immune system and play developmental and physiological roles. Toll-like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases, such as hypertension and heart failure. Since such diseases are commonly accompanied by autonomic imbalance and lower baroreflex sensitivity, we hypothesized that TLR9 modulates cardiac autonomic and baroreflex control of arterial pressure (AP). Toll-like receptor 9 knockout (TLR9 KO) and wild-type (WT) mice were implanted with catheters into carotid artery and jugular vein and allowed to recover for 3 days. After basal recording of AP, mice received methyl-atropine or propranolol. AP and pulse interval (PI) variability were evaluated in the time and frequency domain (spectral analysis), as well as by multiscale entropy. Spontaneous baroreflex was studied by sequence technique. Behavioral and cardiovascular responses to fear-conditioning stress were also evaluated. AP was similar between groups, but TLR9 KO mice exhibited lower basal heart rate (HR). AP variability was not different, but PI variability was increased in TLR9 KO mice. The total entropy was higher in TLR9 KO mice. Moreover, baroreflex function was found higher in TLR9 KO mice. Atropine-induced tachycardia was increased in TLR9 KO mice, whereas the propranolol-induced bradycardia was similar to WT mice. TLR9 KO mice exhibit increased behavioral and decreased tachycardia responses to fear-conditioning stress. In conclusion, our findings suggest that TLR9 may negatively modulate cardiac vagal tone and baroreflex in mice.

Topics: Animals; Arterial Pressure; Atropine Derivatives; Baroreflex; Behavior, Animal; Bradycardia; Cardiovascular System; Conditioning, Psychological; Disease Models, Animal; Fear; Heart Rate; Immunity, Innate; Male; Mice, Inbred C57BL; Mice, Knockout; Propranolol; Signal Transduction; Tachycardia; Time Factors; Toll-Like Receptor 9; Vagus Nerve

It is thought that cardiovascular changes may contribute to sudden death in patients with epilepsy. To examine cardiovascular alterations that occur during epileptogenesis, we measured the heart rate of rats submitted to the electrical amygdala kindling model. Heart rate was recorded before, during, and after the induced seizures. Resting heart rate was increased in stages 1, 3, and 5 as compared with the unstimulated control condition. In the initial one third of the seizures, we observed bradycardia, which increased in intensity with increasing stage and was blocked by injecting methyl atropine. During stage 5 seizures, a rebound tachycardia was observed that also increased in intensity with increasing number of seizures. This study demonstrated the influence of seizure frequency on cardiac autonomic modulation, providing a basis for discussion of potential mechanisms that cause patients with epilepsy to die suddenly.

Topics: Amygdala; Analysis of Variance; Animals; Atropine Derivatives; Disease Models, Animal; Electric Stimulation; Electrocardiography; Electroencephalography; Heart Rate; Kindling, Neurologic; Male; Parasympatholytics; Rats; Rats, Wistar; Reaction Time; Seizures; Tachycardia

The present study was undertaken to compare the effects of chronic hyperinsulinemia with or without insulin resistance on the autonomic control of heart rate (HR) in rats.. Male Sprague-Dawley rats were implanted subcutaneously with insulin (3 mU/kg x min) or vehicle-filled osmotic minipumps for 8 weeks. Insulin-infused rats were further divided into insulin resistant (IR) and insulin sensitive (IS) groups according to the results of the homeostasis model assessment method and euglycemic hyperinsulinemic clamp study. Autonomic function in HR control was indicated by arterial baroreflex sensitivity (BRS) after a bolus injection of phenylephrine or sodium nitroprusside.. Compared with those in control group, plasma insulin levels were elevated about threefold and 1.5-fold in the IR and IS groups at the end of week 8, respectively. Blood glucose level remained basal in the IR group, but was significantly lower in the IS group. The elevated mean arterial pressure (MAP) observed in IR was not exhibited in IS. The HR and BRS in reflex tachycardia were significantly increased in the IR and IS groups, but the BRS in reflex bradycardia was not different among all rats. Propranolol eliminated the tachycardia and enhanced BRS responses in both groups. Methylatropine further accelerated tachycardia and diminished the enhanced BRS in the IR group. However, in IS, the enhanced BRS remained after methylatropine was given. The intrinsic HR was similar among all groups. The baseline MAP, HR, and BRS in reflex tachycardia were significantly correlated to plasma insulin levels but not to the Si value, an index of insulin sensitivity.. The present results demonstrate that hyperinsulinemia but not insulin resistance is a dominant contributing factor to the development of arterial baroreflex abnormalities in this chronic hyperinsulinemic model, which may simultaneously enhance sympathetic nerve activity and possibly vagal withdrawal if insulin resistance coexisted.

Topics: Animals; Atropine Derivatives; Autonomic Nervous System; Baroreflex; Blood Glucose; Disease Models, Animal; Heart Rate; Hyperinsulinism; Insulin; Insulin Resistance; Male; Parasympatholytics; Rats; Rats, Sprague-Dawley; Tachycardia; Vagus Nerve

The present study evaluated the possible changes in the autonomic control of heart rate in the hypertensive model induced by the inhibition of nitric oxide synthase. Rats were treated with N(G)-nitro-L-arginine methyl ester (L-NAME group) in the drinking water during 7 days, whereas control groups were treated with tap water (control group) or with the N(G)-nitro-D-arginine methyl ester (D-NAME group), an inactive isomer of the L-NAME molecule. The L-NAME group developed hypertension and tachycardia. The sequential blockade of the autonomic influences with propranolol and methylatropine indicated that the intrinsic heart rate did not differ among groups and revealed a sympathetic overactivity in the control of heart rate in the L-NAME group. The spectral density power of heart rate, calculated using fast-Fourier transformation, indicated a reduced variability in the low-frequency band (0.20-0.60 Hz) for the L-NAME group. The baroreflex sensitivity was also attenuated in these animals when compared with the normotensive control or D-NAME group. Overall, these data indicate cardiac sympathetic overactivity associated with a decreased baroreflex sensitivity in L-NAME hypertensive rats.

Topics: Animals; Antihypertensive Agents; Atropine Derivatives; Baroreflex; Enzyme Inhibitors; Fourier Analysis; Heart; Heart Rate; Hypertension; Male; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Acid; Parasympatholytics; Propranolol; Rats; Rats, Wistar; Sympathetic Nervous System; Tachycardia

Spontaneously diabetic BB/W rats were compared with age-matched regular Wistar and nondiabetic BB/W rats to determine whether the presence of diabetes would alter cardiovascular regulation appreciably. Systolic and mean blood pressures measured with the tail-cuff method from 12 to 26 wk of age tended to be slightly higher in diabetic than nondiabetic BB/W rats, but the differences were not significant. Mean pressures recorded from indwelling catheters in the same rats at 28 wk of age also did not differ significantly, thereby verifying that the diabetic rats were not hypertensive. To measure baroreflex sensitivity, heart-rate responses were elicited reflexly by elevating blood pressure with phenylephrine or lowering it with sodium nitroprusside. Although reflex bradycardia elicited with phenylephrine was the same, reflex tachycardia elicited with sodium nitroprusside was more pronounced in diabetic BB/W than other rats. Underlying autonomic mechanisms were then assessed by repeating the baroreflex tests after either cholinergic blockade with methylatropine or beta-adrenergic blockade with propranolol. Magnitude of reflex bradycardia after inhibition by either cholinergic or beta-adrenergic blockade still did not differ between rat groups but that of reflex tachycardia remained significantly stronger in diabetic BB/W than other rats. These results collectively show that, although diabetic BB/W rats remained normotensive, they had enhanced reflex tachycardia that persisted even after efferent autonomic blockade. The failure to develop higher pressures with time further indicates that without additional manipulation, these rats cannot be used experimentally to simulate the simultaneous presence of hypertension in diabetic patients.

Topics: Adrenergic beta-Antagonists; Animals; Atropine Derivatives; Blood Pressure; Diabetes Mellitus; Heart Rate; Male; Nitroprusside; Parasympatholytics; Phenylephrine; Propranolol; Rats; Rats, Inbred BB; Rats, Inbred Strains; Tachycardia