methylatropine and Hypertension

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

The present study investigated whether baroreflex control of autonomic function is impaired when there is a deficiency in NO production and the role of adrenergic and cholinergic mechanisms in mediating reflex responses. Electrical stimulation of the aortic depressor nerve in conscious normotensive and nitro-l-arginine methyl ester (L-NAME)-induced hypertensive rats was applied before and after administration of methylatropine, atenolol, and prazosin alone or in combination. The hypotensive response to progressive electrical stimulation (5 to 90 Hz) was greater in hypertensive (-27 ± 2 to -64 ± 3 mmHg) than in normotensive rats (-17 ± 1 to -46 ± 2 mmHg), whereas the bradycardic response was similar in both groups (-34 ± 5 to -92 ± 9 and -21 ± 2 to -79 ± 7 beats/min, respectively). Methylatropine and atenolol showed no effect in the hypotensive response in either group. Methylatropine blunted the bradycardic response in both groups, whereas atenolol attenuated only in hypertensive rats. Prazosin blunted the hypotensive response in both normotensive (43%) and hypertensive rats (53%) but did not affect the bradycardic response in either group. Prazosin plus angiotensin II, used to restore basal arterial pressure, provided hemodynamic responses similar to those of prazosin alone. The triple pharmacological blockade abolished the bradycardic response in both groups but displayed similar residual hypotensive response in hypertensive (-13 ± 2 to -27 ± 2 mmHg) and normotensive rats (-10 ± 1 to -25 ± 3 mmHg). In conclusion, electrical stimulation produced a well-preserved baroreflex-mediated decrease in arterial pressure and heart rate in conscious l-NAME-induced hypertensive rats. Moreover, withdrawal of the sympathetic drive played a role in the reflex bradycardia only in hypertensive rats. The residual fall in pressure after the triple pharmacological blockade suggests the involvement of a vasodilatory mechanism unrelated to NO or deactivation of α(1)-adrenergic receptor.

Topics: Angiotensin II; Animals; Aorta; Atenolol; Atropine Derivatives; Baroreflex; Blood Pressure; Electric Stimulation; Heart Rate; Hemodynamics; Hypertension; Male; NG-Nitroarginine Methyl Ester; Parasympatholytics; Prazosin; Rats; Rats, Wistar

Autonomic dysfunction, hypertension and cardiovascular morbidity in end stage renal disease are critically linked, however there are limited models available to investigate this relationship and develop clinical interventions. This study aimed to define the relationship between hypertension and autonomic function in a new rodent model of polycystic kidney disease (PKD). Using measures of heart rate and systolic blood pressure variability (HRV, SBPV), and time domain analysis of cardiac and sympathetic baroreflex function, we compared the Lewis PKD model (LPK) to a Lewis control. Systolic BP and SBPV were significantly higher in LPK vs. Lewis (168+/-7 vs. 131+/-8mm Hg, P

Topics: Animals; Antihypertensive Agents; Atenolol; Atropine Derivatives; Autonomic Nervous System; Baroreflex; Blood Pressure; Cardiovascular System; Disease Models, Animal; Electrophysiologic Techniques, Cardiac; Fourier Analysis; Heart Rate; Hypertension; Male; Nitroprusside; Parasympatholytics; Polycystic Kidney, Autosomal Recessive; Rats; Rats, Inbred Lew; Signal Processing, Computer-Assisted

The nitric oxide (NO) synthesis blockade is characterized by an increase in the cardiac sympathetic activity and the physical training promotes the decrease in the sympathetic activity.. We investigated the effect of the NO synthesis blockade on the autonomic cardiovascular control in rats submitted to aerobic exercises during a 10-week period.. Male Wistar rats were divided in four groups: control rats, treated with chow food and water ad libitum for 10 weeks (CR); control rats, treated with N G-nitro-L-arginine methyl ester (L-NAME) during the last week (CRL); rats trained during 10 weeks on an electrical treadmill (TR); rats trained for 10 weeks and treated with L-NAME during the last week (TRL). The autonomic cardiovascular control was investigated in all groups with the use of a double blockade with methylatropine and propranolol and analysis of variability.. The CRL and TRL groups presented hypertension. The CRL group presented tachycardia and predominance of the sympathetic tonus in heat rate (HR) measurement after the pharmacological autonomic blockade. The TR group presented bradycardia and lower intrinsic HR when compared to the others. The evaluation of the HR variability showed lower absolute and normalized values in the low frequency (LF) band in the CRL group. On the other hand, the TRL presented an increase in the LF band in absolute values. The analysis of variability of the systemic arterial pressure (SAP) showed that the CRL and TRL groups presented higher values in the LF band.. The previous physical exercise prevented the deficit in the autonomic cardiac control induced by the treatment with L-NAME, but did not prevent the increase in the SAP variability.

Topics: Adrenergic beta-Antagonists; Analysis of Variance; Animals; Atropine Derivatives; Autonomic Nervous System; Blood Pressure; Disease Models, Animal; Enzyme Inhibitors; Heart Rate; Hypertension; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Physical Conditioning, Animal; Propranolol; Rats; Rats, Wistar

The autonomic nervous system plays an important role in physiological and pathological conditions, and has been extensively evaluated by parametric and non-parametric spectral analysis. To compare the results obtained with fast Fourier transform (FFT) and the autoregressive (AR) method, we performed a comprehensive comparative study using data from humans and rats during pharmacological blockade (in rats), a postural test (in humans), and in the hypertensive state (in both humans and rats). Although postural hypotension in humans induced an increase in normalized low-frequency (LFnu) of systolic blood pressure, the increase in the ratio was detected only by AR. In rats, AR and FFT analysis did not agree for LFnu and high frequency (HFnu) under basal conditions and after vagal blockade. The increase in the LF/HF ratio of the pulse interval, induced by methylatropine, was detected only by FFT. In hypertensive patients, changes in LF and HF for systolic blood pressure were observed only by AR; FFT was able to detect the reduction in both blood pressure variance and total power. In hypertensive rats, AR presented different values of variance and total power for systolic blood pressure. Moreover, AR and FFT presented discordant results for LF, LFnu, HF, LF/HF ratio, and total power for pulse interval. We provide evidence for disagreement in 23% of the indices of blood pressure and heart rate variability in humans and 67% discordance in rats when these variables are evaluated by AR and FFT under physiological and pathological conditions. The overall disagreement between AR and FFT in this study was 43%.

Topics: Animals; Atropine Derivatives; Autonomic Nervous System; Female; Fourier Analysis; Heart Block; Heart Rate; Humans; Hypertension; Male; Middle Aged; Rats; Rats, Inbred SHR; Rats, Wistar; Severity of Illness Index; Tilt-Table Test; Young Adult

The present study has investigated the effect of blockade of nitric oxide synthesis on cardiovascular autonomic adaptations induced by aerobic physical training using different approaches: 1) double blockade with methylatropine and propranolol; 2) systolic arterial pressure (SAP) and heart rate variability (HRV) by means of spectral analysis; and 3) baroreflex sensitivity.. Male Wistar rats were divided into four groups: sedentary rats (SR); sedentary rats treated with N(omega)-nitro-l-arginine methyl ester (L-NAME) for one week (SRL); rats trained for eight weeks (TR); and rats trained for eight weeks and treated with L-NAME in the last week (TRL).. Hypertension and tachycardia were observed in SRL group. Previous physical training attenuated the hypertension in L-NAME-treated rats. Bradycardia was seen in TR and TRL groups, although such a condition was more prominent in the latter. All trained rats had lower intrinsic heart rates. Pharmacological evaluation of cardiac autonomic tonus showed sympathetic predominance in SRL group, differently than other groups. Spectral analysis of HRV showed smaller low frequency oscillations (LF: 0.2-0.75 Hz) in SRL group compared to other groups. Rats treated with L-NAME presented greater LF oscillations in the SAP compared to non-treated rats, but oscillations were found to be smaller in TRL group. Nitric oxide synthesis inhibition with L-NAME reduced the baroreflex sensitivity in sedentary and trained animals.. Our results showed that nitric oxide synthesis blockade impaired the cardiovascular autonomic adaptations induced by previous aerobic physical training in rats that might be, at least in part, ascribed to a decreased baroreflex sensitivity.

Topics: Adaptation, Physiological; Animals; Atropine Derivatives; Autonomic Nervous System; Baroreflex; Blood Pressure; Drug Administration Schedule; Enzyme Inhibitors; Heart Rate; Hypertension; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Parasympatholytics; Propranolol; Rats; Rats, Wistar; Spectrum Analysis; Vasodilator Agents

We have investigated the ovariectomy effects on the cardiovascular autonomic adaptations induced by aerobic physical training and the role played by nitric oxide (NO). Female Wistar rats (n=70) were divided into five groups: Sedentary Sham (SS); Trained Sham (TS); Trained Hypertensive Sham treated with N(G)-nitro-L-arginine methyl ester (L-NAME) (THS); Trained Ovariectomized (TO); and Trained Hypertensive Ovariectomized treated with L-NAME (THO). Trained groups were submitted to a physical training during 10 weeks. The cardiovascular autonomic control was investigated in all groups using different approaches: 1) pharmacological evaluation of autonomic tonus with methylatropine and propranolol; 2) analysis of heart rate (HR) and systolic arterial pressure (AP) variability; 3) spontaneous baroreflex sensitivity (BRS) evaluation. Hypertension was observed in THS and THO groups. Pharmacological analysis showed that TS group had increased predominance of autonomic vagal tonus compared to SS group. HR and intrinsic HR were found to be reduced in all trained animals. TS group, compared to other groups, showed a reduction in LF oscillations (LF=0.2-0.75 Hz) of pulse interval in both absolute and normalized units as well as an increase in HF oscillations (HF=0.75-2.50 Hz) in normalized unit. BRS analysis showed that alpha-index was different between all groups. TS group presented the greatest value, followed by the TO, SS, THO and THS groups. Ovariectomy has negative effects on cardiac autonomic modulation in trained rats, which is characterized by an increase in the sympathetic autonomic modulation. These negative effects suggest NO deficiency. In contrast, the ovariectomy seems to have no effect on AP variability.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Analysis of Variance; Animals; Atropine Derivatives; Autonomic Nervous System; Baroreflex; Blood Pressure; Cardiovascular System; Female; Heart Rate; Hypertension; Injections, Intravenous; NG-Nitroarginine Methyl Ester; Nitric Oxide; Ovariectomy; Parasympatholytics; Physical Conditioning, Animal; Propranolol; Rats; Rats, Wistar

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

The acetylcholinesterase inhibitor, soman, induces marked and sustained hypertension and tachycardia associated with a convulsive syndrome in rats. The aims of the present study were to distinguish between the cardiovascular and convulsant effects of soman and to determine whether the maintenance of the soman-induced hypertension and tachycardia depends solely on a central muscarinic effect. To this end, using a computerised analysis of blood pressure (BP) in conscious freely moving rats, we examined the consequences on the increase in mean BP (MBP) and heart rate (HR) induced by soman (60 micrograms/kg, i.v.) of 1) a pre-treatment with the anticonvulsant drug diazepam (3 mg/kg, i.v.) and 2) atropine sulphate (10 mg/kg, i.v.) administered 10 or 60 min after the intoxication. Pretreatment with diazepam prevented the convulsions, assessed by electroencephalogram (EEG) recording, but modified neither the magnitude nor the kinetics of the pressor and tachycardic effects of soman (delta MBP = 74 +/- 2 and 73 +/- 5 mmHg, delta HR = 69 +/- 10 and 79 +/- 7 bpm, maximum MBP = 186 +/- 3 and 182 +/- 6 mmHg, maximum HR = 545 +/- 9 and 522 +/- 16 bpm in solvent- (n = 8) and diazepam- (n = 8) pre-treated rats, respectively). Whatever its time of administration, atropine sulphate fully and immediately reversed the rise in BP induced by soman. The soman-induced tachycardia was also suppressed by atropine administered 10 min after soman whereas it persisted when atropine was injected 60 min after the intoxication. These results show that the cardiovascular effects of soman can occur independently of the convulsive syndrome and that the maintenance of the soman-induced hypertension depends entirely on a permanent central muscarinic stimulation.

Topics: Animals; Anticonvulsants; Atropine; Atropine Derivatives; Blood Pressure; Brain; Cholinesterase Inhibitors; Diazepam; Electroencephalography; Heart Rate; Hypertension; Male; Muscarinic Antagonists; Rats; Rats, Wistar; Seizures; Soman

The influence of daily spontaneous running (DSR) and gender on postexercise cardiac autonomic responses was examined in spontaneously hypertensive rats. Rats were weaned at 4-5 wk of age and were randomly assigned to a sedentary (7 males and 6 females) or DSR (7 males and 8 females) group. After 8 weeks of DSR or sedentary control, rats were chronically instrumented with arterial and venous catheters. After 5 days of recovery, cardiac sympathetic (ST) and parasympathetic tonus (PT) were determined (by the response of heart rate to receptor antagonists) on alternate days under two experimental conditions: no exercise and postexercise. After a single bout of dynamic treadmill exercise (12 m/min, 10% grade for 40 min) ST was reduced (P < 0.05) (male sedentary: no exercise 45 +/- 4 vs. postexercise 28 +/- 3 beats/min; female sedentary: no exercise 69 +/- 10 vs. postexercise 37 +/- 7 beats/ min). PT was also altered after exercise (male sedentary: no exercise -31 +/- 4 vs. postexercise -11 +/- 2 beats/min; female sedentary: no exercise -5 +/- 4 vs. postexercise 7 +/- 4 beats/min). After DSR, ST was reduced (male sedentary 45 +/- 4 vs. DSR 22 +/- 3 beats/min; female sedentary 69 +/- 10 vs. DSR 36 +/- 4 beats/min) (P < 0.05). Finally, male rats had a lower ST and higher PT than female rats. These results demonstrate that 1) ST was reduced after a single bout of dynamic exercise; 2) ST was reduced after DSR; 3) the autonomic response to acute exercise was attenuated after DSR; and 4) there was a gender influence on the cardiac autonomic function.

Topics: Animals; Atropine Derivatives; Autonomic Nervous System; Exercise Test; Female; Heart; Heart Rate; Hypertension; Male; Metoprolol; Nitroglycerin; Phenylephrine; Physical Conditioning, Animal; Rats; Rats, Inbred SHR; Running; Sex Characteristics; Sympathetic Nervous System; Weight Loss

The aim of the study was to test whether circadian and ultradian variations of cardiac output (CO) in spontaneously hypertensive rats (SHR) differ from those in normotensive Wistar-Kyoto rats (WKY). Twenty-four-hour beat-to-beat recordings of CO (by electromagnetic flow probe) and mean arterial pressure (MAP) were performed in the absence and presence of cardiac autonomic blockade with metoprolol and atropine methylnitrate. Ultradian variability was analyzed by spectral analysis on beat-to-beat data series (high-frequency range) and on averaged minute-to-minute data series (low-frequency range). In general, circadian and ultradian rhythms of CO were similar in SHR (n = 10) and WKY (n = 9). Values of CO were high during the dark and low during the light period, whereas total peripheral resistance was highest during the light period. During cardiac autonomic blockade, relative differences between averaged values of CO over the dark and light periods were reduced. High-frequency spectral power of CO was mainly confined to fluctuations related to respiration and was not influenced by cardiac autonomic blockade. At low-frequency ranges, power spectra of CO lacked a dominant oscillator but showed 1/f characteristics. During cardiac autonomic blockade, low-frequency spectral power of CO fell without changing the 1/f characteristics. These findings suggest that dynamic control of CO is not altered in SHR and that autonomic effects on CO are frequency dependent. In most frequency ranges, the relative variation of CO was higher than that of MAP. Thus, over 24 h in both adult SHR and WKY, MAP is controlled within a more narrow range than CO.

Topics: Activity Cycles; Animals; Atropine Derivatives; Blood Pressure; Cardiac Output; Circadian Rhythm; Heart Rate; Hemodynamics; Hypertension; Male; Metoprolol; Parasympatholytics; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke Volume; Vascular Resistance

Acute and chronic exercise decrease peripheral sympathetic nerve activity, but the effect of exercise training of varying intensity on the sympathetic control of heart rate of spontaneously hypertensive rats has not yet been described. The effect of low and high intensities of exercise training on the vagal and sympathetic activities that control heart rate at rest and during dynamic exercise at 0.5, 0.8, and 1.0 mph for 4 minutes per stage was investigated in sedentary (SED, n = 11), high-intensity (HT, n = 12), and low-intensity exercise-trained (LT, n = 13) spontaneously hypertensive rats. Exercise training was performed on a treadmill for 60 minutes, 5 days per week for 18 weeks, at 55% maximum oxygen consumption for the LT group and 85% for the HT group. Vagal and sympathetic activities were studied after administration of methylatropine (3 mg/kg) and propranolol (4 mg/kg), respectively. The LT group had a significantly lower heart rate (at 0.5, 0.8, 1.0 mph versus rest: 410 +/- 7, 464 +/- 9, and 295 +/- 6 beats per minute [bpm], respectively) than the HT (440 +/- 6, 453 +/- 7, 474 +/- 5, and 315 +/- 4 bpm) and the SED (474 +/- 11, 500 +/- 11, 523 +/- 10, and 327 +/- 3 bpm) groups. Sympathetic effect (LT: 84 +/- 10, 88 +/- 12, 105 +/- 12, and 9 +/- 4; HT: 123 +/- 8, 125 +/- 7, 133 +/- 7, and 34 +/- 7; SED: 130 +/- 13, 143 +/- 12, 150 +/- 10, and 38 +/- 7 bpm) and sympathetic tonus (LT: 125 +/- 6, 121 +/- 5, 112 +/- 6, and 91 +/- 6; HT: 145 +/- 9, 136 +/- 6, 142 +/- 8, and 118 +/- 7; SED: 136 +/- 6, 129 +/- 6, 132 +/- 7, and 118 +/- 8 bpm) were significantly decreased by low-intensity exercise training. In conclusion, low- but not high-intensity exercise training causes resting bradycardia and attenuation of tachycardiac response during progressive dynamic exercise in spontaneously hypertensive rats. This effect can be attributed to a significantly decreased beta-adrenergic tone that controls heart rate.

Topics: Animals; Atropine Derivatives; Blood Pressure; Heart; Heart Rate; Hypertension; Male; Oxygen Consumption; Parasympatholytics; Physical Conditioning, Animal; Physical Exertion; Propranolol; Rats; Rats, Inbred SHR; Receptors, Adrenergic, beta; Sympathetic Nervous System; Sympatholytics; Time Factors; Vagus Nerve

To test the hypothesis that impaired baroreflex control of heart rate in Dahl salt-sensitive (S) rats is due to an impairment of the parasympathetic limb of the bradycardic response, baroreflex sensitivity was evaluated in conscious, chronically instrumented Dahl S and salt-resistant (R) animals. Sensitivity was impaired in Dahl S rats when bolus doses of phenylephrine were administered (0.863 +/- 0.042 vs. 1.43 +/- 0.055 ms/mmHg), but it was not different than in R rats when tested with sodium nitroprusside. When the sensitivities before and after blocking the parasympathetic nervous system with atropine were compared, it was revealed that 82% of the reflex bradycardia resulting from bolus doses of phenylephrine was due to the parasympathetic nervous system, whereas the majority (73%) of the bradycardia induced by 5-min infusions of phenylephrine was due to withdrawal of sympathetic tone. Neither baroreflex sensitivity to infusions of phenylephrine (73% sympathetic) or to infusions after atropine (100% sympathetic) were significantly different between S and R rats. Therefore, the impairment of the heart rate reflex in Dahl S rats is due to an impairment of the parasympathetic limb of the response. In addition, a high-salt diet before the development of hypertension did not alter baroreflex sensitivity in either Dahl S or R rats.

Topics: Animals; Atropine Derivatives; Blood Pressure; Dose-Response Relationship, Drug; Heart Rate; Hypertension; Injections; Male; Parasympathetic Nervous System; Parasympatholytics; Rats; Sodium Chloride; Sodium, Dietary; Sympathetic Nervous System

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.

Topics: Animals; Arginine Vasopressin; Atropine Derivatives; Autonomic Nervous System; Blood Pressure; Bradycardia; Carbachol; Cardiovascular Physiological Phenomena; Cardiovascular System; Deamino Arginine Vasopressin; Hypertension; Injections, Intraventricular; Male; Nicotine; Parasympatholytics; Phentolamine; Physostigmine; Rats; Rats, Brattleboro; Vasopressins

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

The cardiovascular effects of centrally administered 5-hydroxytryptamine (5-HT) have been analysed in conscious normotensive and hypertensive rats. In conscious normotensive rats, 5-HT, (1-30 micrograms) administered intracerebroventricularly (i.c.v.) produced profound and immediate dose-related decreases in heart rate and small increases in blood pressure. The initial pressor responses were followed by secondary secondary depressor responses at high doses of 5-HT. Similar effects were produced by 5-HT i.c.v. in conscious DOCA-salt and spontaneously hypertensive rats, although the magnitude of the pressor responses was substantially greater in hypertensive than normotensive rats. Pretreatment with either N-methylatropine or atenolol intra-arterially reduced the 5-HT-induced bradycardia in normotensive rats; the reduction was enhanced when both antagonists were given in combination. The 5-HT2 antagonist, cyproheptadine (10 micrograms i.c.v.) increased basal blood pressure and heart rate in normotensive rats. Subsequent administration of 5-HT i.c.v. produced biphasic effects on heart rate consisting of an initial tachycardia followed by a marked bradycardia. Methysergide (10 micrograms i.c.v.) pretreatment did not alter resting heart rate, but attenuated the 5-HT induced bradycardia. A higher dose of methysergide, (30 micrograms i.c.v.), decreased resting blood pressure and heart rate. This study has demonstrated, therefore, that the 5-HT induced bradycardia is produced by not only a centrally mediated decrease in sympathetic tone, but also an increase in vagal drive to the heart. The bradycardia is antagonised by centrally administered methysergide, but not by cyproheptadine, which suggests that it is probably mediated through a '5-HT1-like' receptor mechanism.

Topics: Animals; Atenolol; Atropine Derivatives; Blood Pressure; Bradycardia; Drug Interactions; Heart; Heart Rate; Hypertension; Injections, Intravenous; Male; Methysergide; Rats; Serotonin; Serotonin Antagonists

The present study describes developmental changes in autonomic controls of heart rate in a strain of rats genetically predisposed to hypertension (spontaneously hypertensive rats or SHR) and in a normotensive strain of rats (Wistar-Kyoto rats or WKY). Rat pups were tested at 4, 8, 12, and 16 days to determine heart rate changes after selective pharmacological treatments. Specifically, freely moving pups were treated with selective beta-adrenergic and muscarinic receptor blockers (i.e., atenolol and atropine methylnitrate), using procedures designed to produce minimal pain or discomfort. The results indicated that by 4 days of age there is a substantial sympathetic acceleratory influence on heart rate. Comparison of inferred autonomic control of the heart in prehypertensive SHR and normotensive WKY pups suggested exaggeration of this early sympathetic influence among SHR pups. After 2 wk of age, however, equivalent autonomic control of heart rate was seen in SHR and WKY rats, with the higher basal heart rate of SHR rats being mediated by an increased intrinsic heart rate (i.e., heart rate after combined blockade). These findings suggest that enhanced sympathetic nervous system activity may be an early expression of the genetic predisposition to develop hypertension.

Topics: Adrenergic beta-Antagonists; Age Factors; Animals; Atenolol; Atropine Derivatives; Autonomic Nervous System; Female; Heart Rate; Hypertension; Male; Parasympatholytics; Rats; Rats, Inbred Strains

Individual differences in cardiovascular regulation result from a dynamic interaction between genetically programmed developmental processes and extrinsic (environmental) conditions. The alterations in autonomic functioning previously identified among pups of the spontaneously hypertensive rat (SHR) strain suggest a genetic influence on autonomic development. In the present studies, an early stimulation procedure previously shown to reduce the behavioral and endocrine responsiveness of rodents in adulthood was demonstrated to alter both neural control of heart rate and regional brain catecholamine levels during the preweaning period. Pups from litters of SHR and Wistar-Kyoto (WKY) rats were handled daily during the first postnatal week. Selective pharmacological blockade with atenolol and atropine methylnitrate was used to identify autonomic controls of heart rate at 16 and 28 days of age. Combined blockade was used to estimate intrinsic heart rate. In both SHR and WKY, early handling was associated with elevated basal heart rate, elevated intrinsic heart rate, and decreased sympathetic tone. Parasympathetic influence on heart rate was elevated by early handling in WKY and decreased by handling in SHR. In addition, an increase in dorsal cortical norepinephrine concentration was produced by early handling in both strains. These data suggest that early environmental conditions can interact with the genetic predisposition for elevated blood pressure and may play a potentially important role in organizing the neural controls of cardiovascular regulation.

Topics: Adrenergic beta-Antagonists; Animals; Atenolol; Atropine Derivatives; Autonomic Nervous System; Brain; Female; Heart Rate; Hypertension; Male; Norepinephrine; Parasympatholytics; Rats; Rats, Inbred Strains; Species Specificity; Weaning

Baroreflex control of heart rate in response to phenylephrine was studied in conscious Sabra hypertension-prone (SBH) rats, at a prehypertensive stage, and hypertension-resistant (SBN) rats. Baroreflex sensitivity as determined from the slope of the relationship of mean arterial blood pressure and heart period was significantly lower in SBH rats (0.58 +/- 0.06 versus 1.71 +/- 0.11 ms/mmHg in SBN rats, P less than 0.01) before the development of hypertension. Sympathetic nerve blockade with guanethidine (15 mg/kg) significantly reduced the slope of the mean arterial blood pressure-heart period relationship in SBN rats to 0.45 +/- 0.05 ms/mmHg (P less than 0.01) and increased the pressor response to phenylephrine, without having any effect on these parameters in SBH rats. Atropine methyl nitrate (1 mg/kg) abolished reflex vagal bradycardia in response to phenylephrine in both groups of rats. This suggests that SBH rats are unable to withdraw the sympathetic cardiac component of the baroreflex in response to a pressor stimulus and appear to rely only on increased vagal activity to effect bradycardia.

Topics: Animals; Atropine Derivatives; Blood Pressure; Guanethidine; Heart Rate; Hypertension; Male; Phenylephrine; Pressoreceptors; Rats; Reflex; Sympathetic Nervous System; Vagus Nerve