Role of autonomic nervous system on heart rate in experimental hypertension

Heart rate and the role of the autonomic nervous system in hypertensive conscious rats by subtotal nephrectomy were studied. Heart rate is significantly higher in the hypertensive rats. Sympathetic blockade with an intravenous injection of propranolol produces a higher decrease in heart rate of hypertensive rats than in control rats. Intravenous injection of atropine produces an increase in heart rate in both groups of animals. It is significantly higher in the control rats than in hypertensive animals. When the autonomic nervous system is blocked with atropine and propranolol, intrinsic heart rate is similar in both groups of animals. Similar results are obtained after blocking ganglionic transmission with hexamethonium. No significative differences are observed in heart rate after intracerebroventricular injection of hemicholinium-3 between both groups of rats. Results show an increased cardiac sympathetic tone, reduced parasympathetic activities, no alterations in the pacemaker activity and implications of central acetylcholine. These alterations in the autonomic nervous system have an important role in the maintenance of elevated heart rate in this experimental model of arterial hypertension.     

Genetic selection on a behavioural fear trait is associated with changes in heart rate variability in quail

This study investigated whether genetic selection on a divergent behavioural trait of fearfulness (tonic immobility duration) was related to changes in the nervous control of the heart. Quail selected for either long or short tonic immobility (LTI or STI, respectively) duration was compared with an unselected control line (CTI). The autonomic control of the heart was assessed by heart rate variability analysis and pharmacological blockades. Quail were surgically fitted with a telemetric device. Heart rate before injection did not differ between the three lines. The vagal-sympathetic effect (VSE) at rest differed significantly from 1 in CTI and STI quail, suggesting that parasympathetic activity was dominant. In LTI quail, VSE did not differ from 1, suggesting a balance between parasympathetic and sympathetic activities. The intrinsic heart rate reached after the successive injections of propranolol and atropine did not differ between lines and was higher than the heart rate at rest in STI, which was in line with results of VSE at rest. After atropine injection, the sympathetic activity indicated by the low-frequency power was lower in CTI than in the two selected quail. After propranolol injection, the parasympathetic activity indicated by the root of the mean squares of successive differences and the high-frequency power was higher in STI than in CTI and LTI quail. Selection on tonic immobility duration thus appears to be associated with changes in the sympathovagal control of the heart, which may influence behavioural responses to stressful situations.     

Autonomic control in rats with overactivity of tissue renin-angiotensin or kallikrein-kinin system

The renin-angiotensin system (RAS) plays an important role in the regulation of the cardiovascular system and the kallikrein-kinin system (KKS) appears to counteract most of the RAS effects. In this study the vagal and the sympathetic influences on the heart rate and the baroreflex control of the heart rate were evaluated in transgenics rats with human tissue kallikrein gene expression [TGR(hKLK1)], and transgenics rats with tissue renin overexpression [TGR(mREN2)27]. Heart rate was similar in all groups but mean arterial pressure was higher in mREN2 rats than in kallikrein and control rats (149+/-4 vs. 114+/-3 vs. 113+/-3 mm Hg, respectively). The intrinsic heart rate was lower in mREN2 rats than in kallikrein and control rats (324+/-5 vs. 331+/-3 vs. 343+/-7 bpm). The HR response to atropine was similar but the response to propranolol was higher in kallikrein rats than control group (61+/-7 vs. 60+/-9 vs. 38+/-7 bpm, respectively). The vagal tonus was lower in mREN2 than in SD and hKAL rats (18+/-3 vs. 40+/-6 vs. 35+/-6 bpm) whereas the sympathetic tonus was higher in kallikrein rats (118+/-7 vs. 96+/-1 vs. 81+/-9 bpm in the mREN2 and SD rats), respectively. Baroreflex sensitivity to bradycardic responses was attenuated in mREN2 rats (0.37+/-0.05 vs. 1.34+/-0.08 vs. 1.34+/-0,13 bpm/mm Hg) while the tachycardic responses were unchanged. The bradycardic responses to electrical stimulation of the vagal nerve were depressed in both renin and kallikrein rats (129+/-47 vs. 129+/-22 vs. 193+/-25 bpm in control group in response to 32 Hz). In conclusion: 1.The rats with overexpression of renin showed decreased intrinsic heart rate and impairment of vagal function, characterized by decreased vagal tonus, reduced response of HR to electrical stimulation of vagus nerve, and depressed reflex bradycardia provoked by increases of blood pressure. 2. The rats with overexpression of kallikrein showed an increase of sympathetic activity that regulates the heart rate, characterized by increased HR response to propranolol and increased sympathetic tonus, accompanied by decreased bradycardic responses to electrical vagal stimulation.     

Autonomic control of heart rate in the adult, aquatic Notophthalmus viridescens viridescens

1. We investigated the role of the autonomic nervous system in the control of the heart rate using an isolated heart preparation. 2. Addition of the parasympathetic blocker, atropine, to the organ bath resulted in an increase in heart rate as expected. 3. Addition of the sympathetic blocker, ergotamine, to the organ bath showed no change in the heart rate. 4. Addition of the sympathetic blocker, propranolol, to the organ bath resulted in the expected decrease in heart rate. 5. Both the sympathetic and parasympathetic nervous systems appear to play a role in the control of the heart rate.     

Sympathetic nervous system representation in time and frequency domain indices of heart rate variability

This study evaluated the contributions of sympathetic and parasympathetic modulation to heart rate variability during situations in which vagal and sympathetic tone predominated. In a placebo-controlled, randomized, double blind blockade study, six young healthy male individuals received propranolol (0.2 mg x kg(-1)), atropine (0.04 mg x kg(-1)), propranolol plus atropine, or placebo infusions over 4 days. Time-domain indices were calculated during 40 min of rest and 20 min of exercise at 70% of maximal exercise intensity. Spectrum analysis, using fast Fourier transformation, was also performed at rest and during the exercise. The time-domain indices standard deviation of R-R intervals, mean of the standard deviations of all R-R intervals for all 5-min segments, percentage of number of pairs of adjacent R-R intervals differing by more than 50 ms, and square root of the mean of the sum of squares of differences between adjacent R-R intervals were reduced after atropine and propranolol plus atropine. Propranolol alone caused no appreciable change in any of the time-domain indices. At rest, all spectrum components were similar after placebo and propranolol infusions, but following parasympathetic and double autonomic blockade there was a reduction in all components of the spectrum analysis, except for the low:high ratio. During exercise, partial and double blockade did not change significantly any of the spectrum components. Thus, time and frequency-domain indices of heart rate variability were able to detect vagal activity, but could not detect sympathetic activity. During exercise, spectrum analysis is not capable of evaluating autonomic modulation of heart rate.     

Baroreceptor mechanisms in rat

Baroreflex control of cardiovascular parameters was studied in control, atropine- and guanethidine-treated rats. Baroreceptor activity was tested by the relationship between the increase in blood pressure produced by a phenylephrine administration (bolus ov infusion) and the induced bradycardia. No differences were observed in basal arterial blood pressure and heart rate between treated- and control rats. Baroreceptor sensitivity was lower in atropine- or guanethidine-treated rats than in control animals. Baroreceptor activity has two components: a first, rapid, predominantly parasympathetic and a second, slower, that is mediated by both parasympathetic and sympathetic efferent pathways.     

Effect of training on the resting heart rate of rats

Adult male rats were progressively trained 5 days/week on a motor-driven treadmill. The training period lasted 12 weeks and consisted of 60 min/day of wind-sprints and endurance work. No significant difference in resting heart rates was observed between the control and exercise groups during week 1 (394±7 vs. 388±5). However, at week 12 the exercise group had a lower resting heart rate (359±6 vs. 331±4). Heart rates observed following saline, propranolol, atropine, and propranolol plus atropine injections were lower in the exercise group in all cases. The difference in heart rates between the control and exercise groups was 19 beats/min following propranolol plus atropine which was less than the 28 beats/min difference observed under control conditions. With atropine and then with propranolol the differences were 33 and 27 beats/min. These heart rate differences were observed without the presence of cardiac hypertrophy as assessed from ventricle weights.Our data indicate that the bradycardia resulting from exercise training is due primarily to changes other than neural influences on the heart.     

Aging and baroreflex control of RSNA and heart rate in rats

Aging is associated with altered autonomic control of cardiovascular function, but baroreflex function in animal models of aging remains controversial. In this study, pressor and depressor agent-induced reflex bradycardia and tachycardia were attenuated in conscious old (24 mo) rats [57 and 59% of responses in young (10 wk) Wistar rats, respectively]. The intrinsic heart rate (HR, 339 +/- 5 vs. 410 +/- 10 beats/min) was reduced in aged animals, but no intergroup differences in resting mean arterial blood pressure (MAP, 112 +/- 3 vs. 113 +/- 5 mmHg) or HR (344 +/- 9 vs. 347 +/- 9 beats/min) existed between old and young rats, respectively. The aged group also exhibited a depressed (49%) parasympathetic contribution to the resting HR value (vagal effect) but preserved sympathetic function after intravenous methylatropine and propranolol. An implantable electrode revealed tonic renal sympathetic nerve activity (RSNA) was similar between groups. However, old rats showed impaired baroreflex control of HR and RSNA after intravenous nitroprusside (-0.63 +/- 0. 18 vs. -1.84 +/- 0.4 bars x cycle(-1) x mmHg(-1) x s(-1)). Therefore, aging in rats is associated with 1) preserved baseline MAP, HR, and RSNA, 2) impaired baroreflex control of HR and RSNA, and 3) altered autonomic control of resting HR.     

Autonomic control of heart rate in the neonatal rhesus monkey

Autonomic control of resting heart rate was assessed using atropine and propranolol in 20 neonatal (2 to 3 weeks old) male Rhesus monkeys. After release from restraint for placement of a venous catheter, the average heart rate significantly decreased from 220 +/- 7 beats/min to 181 +/- 6 beats/min within 15 minutes and remained stable for the 2 hours. Autonomic control of resting heart rate is mediated through both divisions of the autonomic nervous system with the sympathetic system having a dominant influence. This is in contrast to the adult Rhesus, where the parasympathetic nervous system controls resting heart rate.     

Low and nonrhythmic heart rate of the mole rat (Spalax ehrenbergi): Control by the autonomic nervous system

Summary ECG of mole rats (Spalax ehrenbergi) was recorded by chronically implanted electrodes. The average heart rate of unrestrained, resting animals (mean body mass 191 g±35 S.D.) in normoxia and at room temperature is 152 beats/min±42 S.D. It is nonrhythmic and about one third of the rate expected for an animal of this mass. ECG revealed that each heart beat is normal. From atropine and propranolol administration, it was evident that the low heart rate results from : (a) low intrinsic heart rate (285 b/min±30 S.D.), (b) high parasympathetic tone (51%±12 S.D.) and (c) low sympathetic tone (3.6%±1.6 S.D.). Unilateral vagotomy showed that the degree of left or right vagus dominancy in the mole rat differs in each individual: it may even reach a complete left vagus control, in contrast to other mammals where right vagus dominancy is apparent.     

The autonomic nervous control of heart rate in ducks during voluntary diving

Autonomic nervous control of heart rate was studied in voluntarily diving ducks (Aythya affinis). Ducks were injected with the muscarinic blocker atropine, the beta-adrenergic blocker nadolol, the beta-adrenergic agonist isoproterenol, and a combination of both atropine and nadolol. Saline injection was used as a control treatment. The reduction in heart rate (from the predive level) normally seen during a dive was abolished by atropine. Nadolol reduced heart rate during all phases of diving activity-predive, dive, and postdive-indicating that sympathetic output to the heart was not withdrawn during diving. Isoproterenol increased heart rate before, during, and after the dive, although the proportional increase in heart rate was not as high during the dive as compared with the increase in routine heart rate or heart rate during the predive or postdive phase. The parasympathetic system predominates in the control of heart rate during diving despite the maintenance of efferent sympathetic influences to the heart, perhaps due to accentuated antagonism between the two branches of the autonomic nervous system.     

Atrial natriuretic factor stimulates exocrine pancreatic secretion in the rat through NPR-C receptors

Increasing evidence supports the role of atrial natriuretic factor (ANF) in the modulation of gastrointestinal physiology. The effect of ANF on exocrine pancreatic secretion and the possible receptors and pathways involved were studied in vivo. Anesthetized rats were prepared with pancreatic duct cannulation, pyloric ligation, and bile diversion into the duodenum. ANF dose-dependently increased pancreatic secretion of fluid and proteins and enhanced secretin and CCK-evoked response. ANF decreased chloride secretion and increased the pH of the pancreatic juice. Neither cholinergic nor adrenergic blockade affected ANF-stimulated pancreatic secretion. Furthermore, ANF response was not mediated by the release of nitric oxide. ANF-evoked protein secretion was not inhibited by truncal vagotomy, atropine, or Nomega-nitro-l-arginine methyl ester administration. The selective natriuretic peptide receptor-C (NPR-C) receptor agonist cANP-(4-23) mimicked ANF response in a dose-dependent fashion. When the intracellular signaling coupled to NPR-C receptors was investigated in isolated pancreatic acini, results showed that ANF did not modify basal or forskolin-evoked cAMP formation, but it dose-dependently enhanced phosphoinositide hydrolysis, which was blocked by the selective PLC inhibitor U-73122. ANF stimulated exocrine pancreatic secretion in the rat, and its effect was not mediated by nitric oxide or parasympathetic or sympathetic activity. Furthermore, CCK and secretin appear not to be involved in ANF response. Present findings support that ANF exerts a stimulatory effect on pancreatic exocrine secretion mediated by NPR-C receptors coupled to the phosphoinositide pathway.     

Intracerebroventricular injection of hemicholinium-3 lowers blood pressure in conscious spontaneously hypertensive rats but not in normotensive rats

Intracerebroventricular (icv) injection of hemicholinium-3 (HC-3) in doses of 10–20 μg causes a dose-related decrease in the blood pressure of conscious spontaneous hypertensive (SH) rats but not of normotensive rats. HC-3 also reduces heart rate (HR) in both SH and normotensive rats. The bradycardia was blocked by intravenous injection of methylatropine, implicating increased vagal activity as a cause of the response. The decrease in HR also was blocked by icv injection of atropine but not by icv injection of mecamylamine, suggesting that the bradycardia is mediated via central muscarinic receptors. In contrast, the fall in blood pressure in SH rats was not influenced by intravenous administration of methylatropine or by the icv injection of either atropine or mecamylamine.     

Capsaicin increases modulation of sympathetic nerve activity in rats: measurement using power spectral analysis of heart rate fluctuations

We assessed the sympatho-vagal activities of the heart after administration of capsaicin by measuring the power spectral analysis in rats. There were major two frequency components of heart rate variability, which we defined as high (1.0 Hz <, HF) and low (LF, < 1.0 Hz) frequency components. Vagal blockade by atropine abolished the high frequency component, and lowered the amplitude of the low frequency component. On the other hand, under conditions of sympathetic blockade by propranolol, the low frequency component was reduced. Combined vagal and sympathetic blockade abolished all heart rate fluctuations. We analyzed the low and high frequency components by integrating the spectrum for the respective band width. The rats administered capsaicin had a higher heart rate and sympathetic nervous system index (LF/HF) than the control group of rats. These results suggest that power spectral analysis is an effective and noninvasive method for detecting subtle changes in autonomic activity in response to the intake of foods or drugs.     

Nonuniformity in the von Bezold-Jarisch reflex

The von Bezold-Jarisch reflex (BJR) is a vagally mediated chemoreflex from the heart and lungs, causing hypopnea, bradycardia, and inhibition of sympathetic vasomotor tone. However, cardiac sympathetic nerve activity (CSNA) has not been systematically compared with vasomotor activity during the BJR. In 11 urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats, we measured CSNA simultaneously with lumbar sympathetic activity (LSNA) while the BJR was evoked by right atrial bolus injections of phenylbiguanide (0.5, 1.0, 1.5, and 2 microg). Nerve and heartbeat responses were analyzed by calculating normalized cumulative sums. LSNA and heartbeats were always reduced by the BJR. An excitatory "rebound" component often followed the inhibition of LSNA but never outweighed it. For CSNA, however, excitation usually (in 7 of 11 rats) outweighed any initial inhibition, such that the net response to phenylbiguanide was excitatory. The differences in net response between LSNA, CSNA, and heartbeats were all significant (P < 0.01). A second experimental series on seven rats showed that methyl atropine (1 mg/kg iv) abolished the bradycardia of the BJR, whereas subsequent bilateral vagotomy substantially reduced LSNA and CSNA responses, both excitatory and inhibitory. These findings show that, during the BJR, 1) CSNA is often excited, 2) there may be coactivation of sympathetic and parasympathetic drives to the heart, 3) divergent responses may be evoked simultaneously in cardiac vagal, cardiac sympathetic, and vasomotor nervous pathways, and 4) those divergent responses are mediated primarily by the vagi.     

Respiratory sinus arrhythmia: noninvasive measure of parasympathetic cardiac control.

The degree of parasympathetic heart rate control, PC, was defined as the decrease in average heart period (RR interval) caused by the elimination of parasympathetically mediated influences on the heart while keeping sympathetic activity unchanged. By reviewing published results on the interaction of sympathetic and parasympathetic heart rate control, the prediction was made that PC should be directly proportional to VHP, the peak-to-peak variations in heart period caused by spontaneous respiration. In sevel chloralose/urethan-anesthetized dogs the vagi were reversibly blocked by cooling, and PC (the difference between average heart period before and after cooling) and VHP (without cooling) were determined under a variety of conditions that included a) increasing vagal activity by elevating the blood pressure b) sympathetic blockade, and c) parasympathetic blockade. The relationship between VHP and PC was linear with an average correlation coefficient of 0.969 +/- 0.024 (SD) and a PC-axis intercept of 15.2 +/- 25.9 ms. In each dog the correlation coefficient between VHP and PC was higher than between VHP and the average heart period (avg correlation coef: 0.914 +/- 0.044). These results suggest that the degree of respiratory sinus arrhythmia may be used as a noninvasive indicator of the degree of parasympathetic cardiac control.     

Peripheral nervous control of cold-induced reduction in the respiratory quotient of the rat

Cold-exposed rats show a reduction in the respiratory quotient which is indicative of a relative shift from carbohydrates to lipids as substrates for oxidative metabolism. In the present study, the effects of food deprivation and cold exposure on the respiratory quotient were observed. In addition, the involvement of the three main branches of the peripheral nervous system (sympathetic, parasympathetic, and somatic) was investigated by means of synaptic blockade with propranolol, atropine, and quinine, respectively. Both propranolol and quinine blocked the cold-induced decrease in respiratory quotient and increase in heat production, whereas atropine had only minor and very brief effects. It is concluded that both the sympathetic and somatic branches are involved in the metabolic changes associated with cold-induced thermogenesis and that the increase in metabolic heat production involves a shift from carbohydrate to lipid utilization irrespective of which of the two branches is activated.     

Capsaicin Increases Modulation of Sympathetic Nerve Activity in Rats: Measurement Using Power Spectral Analysis of Heart Rate Fluctuations

We assessed the sympatho-vagal activities of the heart after administration of capsaicin by measuring the power spectral analysis in rats. There were major two frequency components of heart rate variability, which we defined as high (1.0 Hz<, HF) and low (LF, <1.0 Hz) frequency components. Vagal blockade by atropine abolished the high frequency component, and lowered the amplitude of the low frequency component. On the other hand, under conditions of sympathetic blockade by propranolol, the low frequency component was reduced. Combined vagal and sympathetic blockade abolished all heart rate fluctuations. We analyzed the low and high frequency components by integrating the spectrum for the respective band width. The rats administered capsaicin had a higher heart rate and sympathetic nervous system index (LF/HF) than the control group of rats. These results suggest that power spectral analysis is an effective and noninvasive method for detecting subtle changes in autonomic activity in response to the intake of foods or drugs.     

Regulation of cardiac rhythm in hibernating mammals

The dramatic fall in heart rate exhibited by mammals entering hibernation begins before there is any noticeable fall in body temperature. The initial, progressive decrease in heart rate is the result of a cyclic parasympathetic activation that induces skipped beats and regular asystoles as well as slows the even heart beat. As body temperature subsequently falls, the parasympathetic influence is progressively withdrawn and periods of parasympathetic and sympathetic dominance alternate and give rise to regular periods of arrhythmia (tachycardia followed by bradycardia), and occasional long asystoles or periods of highly irregular cardiac activity. Superimposed on this is a vagally-mediated, respiratory sinus arrhythmia that is accentuated in species that breathe episodically. These events give way to a uniform heart rate in deep hibernation at low temperatures where both parasympathetic and sympathetic tone appear absent. The complete absence of tone is not a function of reduced temperature but is reflective of the state of deep, steady state hibernation. The elevation in heart rate that accompanies the onset of arousal is the result of dramatic increases in sympathetic activation that precede any increases in body temperature. As body temperature then rises, sympathetic influence is slowly withdrawn. Arrhythmias are also common during natural arousals or shifts from lower to warmer hibernation temperatures as periods of parasympathetic and sympathetic dominance again alternate en route to re-establishing a steady state in euthermia. The mechanism behind, and the biological significance of, cardiac changes mediated through orchestrated arrhythmias remain unknown.     

Pyridostigmine Restores Cardiac Autonomic Balance after Small Myocardial Infarction in Mice

The effect of pyridostigmine (PYR) - an acetylcholinesterase inhibitor - on hemodynamics and cardiac autonomic control, was never studied in conscious myocardial infarcted mice. Telemetry transmitters were implanted into the carotid artery under isoflurane anesthesia. Seven to ten days after recovery from the surgery, basal arterial pressure and heart rate were recorded, while parasympathetic and sympathetic tone (ΔHR) was evaluated by means of methyl atropine and propranolol. After the basal hemodynamic recording the mice were subjected to left coronary artery ligation for producing myocardial infarction (MI), or sham operation, and implantation of minipumps filled with PYR or saline. Separate groups of anesthetized (isoflurane) mice previously (4 weeks) subjected to MI, or sham coronary artery ligation, were submitted to cardiac function examination. The mice exhibited an infarct length of approximately 12%, no change in arterial pressure and increased heart rate only in the 1st week after MI. Vagal tone decreased in the 1^st week, while the sympathetic tone was increased in the 1^st and 4^th week after MI. PYR prevented the increase in heart rate but did not affect the arterial pressure. Moreover, PYR prevented the increase in sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR not only impaired its attenuation in the 1^st week, but enhanced it in the 4^th week. MI decreased ejection fraction and increased diastolic and systolic volume. Therefore, the pharmacological increase of peripheral acetylcholine availability by means of PYR prevented tachycardia, increased parasympathetic and decreased sympathetic tone after MI in mice.