Baroreceptor Control Of Heart Rate Research Articles

Simvastatin but not ezetimibe reduces sympathetic activity despite similar reductions in cholesterol levels

The relationship between the sympatholytic effects of statins and their lipid-lowering activity remains unclear. Ezetimibe lowers cholesterol, but its sympatholytic activity is unknown. The purpose of study was to compare the influence of equipotent doses of simvastatin and ezetimibe on sympathetic activity. This randomized double-blinded study was performed in 22 hypertensive patients (age, 45.6 ± 2.2 years; female/male, 2/20) with untreated hypercholesterolemia. The subjects were administered 20 mg/d of simvastatin (n = 11) or 20 mg/d of ezetimibe (n = 11) for 6 weeks. Pre- and post-treatment measurements of muscle sympathetic nerve activity (MSNA), baroreceptor control of heart rate (baroreflex sensitivity), and impedance cardiography were recorded. Simvastatin and ezetimibe produced similar reductions of total (−58.0 ± 23.4 vs. −45.2 ± 17.2 mg/dL; P = .15, respectively) and low-density lipoprotein cholesterol (−52.6 ± 20.9 vs. −37.9 ± 17.6 mg/dL; P = .09, respectively). There was a significant difference in the effect of simvastatin and ezetimibe on muscle sympathetic nerve activity (−8.5 ± 5.1 vs. −0.7 ± 3.5 bursts/min; P = .0005). Simvastatin improved baroreflex sensitivity as compared with ezetimibe (10.0 ± 14.3 vs. −2.8 ± 6.1 ms/mm Hg; P = .01). There was no difference in the effect of both treatments on blood pressure, heart rate, cardiac output, stroke volume, total peripheral resistance, high-density lipoprotein, and triglycerides. Simvastatin reduced sympathetic activity via lipid-independent mechanisms, but ezetimibe exerts no sympatholytic effects.

Deactivation of carotid body chemoreceptors by hyperoxia decreases blood pressure in hypertensive patients

Previous studies have shown that hyperoxia-induced deactivation of carotid body chemoreceptors reduces sympathetic activity in hypertensive patients but it does not affect blood pressure. The maintenance of blood pressure can be explained by the direct, vasoconstrictive effect of hyperoxia, which offsets diminished sympathetic activity. This study compares the effect of acute hyperoxia on hemodynamic parameters between hypertensive and normotensive subjects. Twelve males with hypertension (age 39.4±2.4 years; body mass index 27.4±1.1 kg m(-2)) and 11 normotensive males (age 39.9±2.7 years; body mass index 25.4±0.7 kg m(-2)) received, via non-rebreathing mask ventilation, ambient air, followed by 100% oxygen for 20 min. The stroke volume, heart rate, cardiac output, blood pressure, total peripheral resistance, respiratory rate, baroreceptor control of heart rate and oxygen saturation were recorded continuously. Several 30 s periods were analyzed before, during and after inducing hyperoxia. At baseline, the hypertensive subject's blood pressure was higher and their baroreflex control of heart rate was lower when compared with the normotensive control group. After the first 30 s of hyperoxia, systolic, diastolic and mean blood pressures, as well as the total peripheral resistance, decreased significantly in hypertensives but not in normotensives. After 20 min of 100% oxygen ventilation, systolic and mean blood pressures and total peripheral resistance was increased in hypertensive patients, and the cardiac output and stroke volume had decreased in both groups. The results of this study confirm that deactivation of carotid body chemoreceptors can acutely decrease blood pressure in humans.

Redox imbalances incite the hypertensive, baroreflex, and autonomic effects of cyclosporine in rats

Previous studies including ours showed that cyclosporine (CSA) causes baroreflex dysfunction and hypertension. Here we tested the hypothesis that oxidative damage in central and peripheral tissues underlies the hypertensive, baroreflex and autonomic actions elicited by CSA in rats. We investigated the effects of individual and combined 7-day treatments with CSA (25mg/kg/day, n=7) and 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol, superoxide dismutase mimetic, 100mg/kg/day, n=7) on blood pressure, reflex heart rate responses to peripherally mediated pressor and depressor responses, and biomarkers of oxidative stress. CSA elevated blood pressure and reduced reflex bradycardic (phenylephrine) and tachycardic (sodium nitroptrusside) responses. The ability of muscarinic (atropine, 1mg/kg i.v.) or β-adrenoceptor blockade (propranolol, 1mg/kg i.v.) to reduce reflex heart rate responses was reduced in CSA-treated rats, suggesting the impairment by CSA of reflex cardiac autonomic control. Concurrent administration of tempol abolished CSA-induced hypertension and normalized the associated impairment in baroreflex gain and cardiac autonomic control. Tempol also reversed the CSA-induced increases in aortic and brainstem nitrite/nitrate and malondialdehyde (MDA) and decreases in aortic superoxide dismutase (SOD). These findings implicate oxidative stress in peripheral and central cardiovascular sites in the deleterious actions of CSA on blood pressure and baroreceptor control of heart rate.

Baroreflex control of heart rate and renal sympathetic nerve activity in rats with low brain angiotensinogen

The main objective of the present study was to evaluate baroreceptor control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in transgenic rats (TG) with low angiotensinogen production in glial cells, TGR(ASrAogen)-680. In addition, the sympathetic and vagal autonomic tonus to the heart was investigated. As previously shown, TG rats presented a lower arterial pressure (AP) and HR. However, TG rats had decreased AP variability during the night (8.9+/-0.4 mmHg vs 9.8+/-0.3 mmHg, in SD) accompanied by an increase in HR variability (39+/-1 beats/min vs 35+/-1 beats/min, in SD) and augmented locomotor activity during the night (3.5+/-0.3 counts/min vs 2.5+/-0.2 counts/min, in SD). In addition, TG rats presented increased baroreflex sensitivity for the RSNA (slope of line that correlates decreases in RSNA and increases in AP=1.36+/-0.18 vs 0.77+/-0.1, in SD) and an increased sensitivity for both the baroreflex bradycardia (0.79+/-0.04 ms/mmHg vs 0.52+/-0.04 ms/mmHg, in SD) and tachycardia (1.46+/-0.1 ms/mmHg vs 0.93+/-0.01 ms/mmHg, in SD). Further, TG rats had increased vagal tonus (25+/-3 beats/min vs 11+/-4 beats/min in SD) without significant change in the sympathetic tonus to the heart. These results confirm and extend previous observations showing that glial angiotensinogen, the main source of brain RAS peptides, importantly modulates sympathetic tonus, at least to the renal nerve, and vagal tonus to the heart.

Abnormalities in baroreflex sensitivity and autonomic control in conscious ASIC2 ‐/‐ mice

Acid sensing ion channel 2 (ASIC2) has been implicated as a mechanosensor in sensory nerves (Nature 407:2000). Previously, we demonstrated a blunting of increases in baroreceptor (BR) activity during increases in blood pressure (BP) in ASIC2 deficient (ASIC2−/−) mice, suggesting that ASIC2 contributes to BR mechanoelectrical transduction (FASEB J. 15(5):2001). We hypothesized that a defect in BR sensory function in ASIC2−/−mice will translate into impaired BR control of heart rate (HR), decreased parasympathetic tone, and increased sympathetic tone. BP and HR were measured by telemetry in conscious control (n=6) and ASIC2−/− (n=5) male mice. BR sensitivity (BRS) was calculated from spontaneous reciprocal fluctuations in BP and HR using the sequence method. Resting mean BP was similar in control (98±4 mmHg) and ASIC2−/− (101±5 mmHg) mice, whereas HR was significantly higher in ASIC2−/− mice (552±19 vs. 495±18 bpm, *P<0.05). This pattern was also observed during periods of spontaneous locomotor activity (see table). ASIC2−/− mice exhibited decreased BRS, reduced HR response to methylatropine (parasympathetic tone), and increased HR response to propranolol (sympathetic tone). Taken together with our previous findings, these results support the hypothesis that ASIC2 is a component of the BR mechanosensitive channel complex. (NIH HL14388 and AHA#0525745Z)

Effects of slow, controlled breathing on baroreceptor control of heart rate and blood pressure in healthy men.

Slow, controlled breathing has been shown by cross-spectral techniques to potentiate arterial baroreflex control of heart rate. However, crucial aspects of the effects of slow breathing on the arterial baroreflex remain unsettled, namely whether the major function of the arterial baroreflex (i.e. the control of blood pressure) is also potentiated and whether baroreflex function is differentially modulated according to the age of the individual. To examine the bradycardic and depressor responses to selective carotid baroreceptor stimulation by the neck chamber technique (-15 and -30 mmHg neck suction) and the cross-spectral R-R interval/systolic blood pressure relationship (alpha index). In 24 resting, supine healthy male volunteers (aged 19-66 years, mean +/-SEM 37.5 +/- 3.19 years), blood pressure (Finapres), R-R interval (electrocardiogram) and ventilation (impedance) were recorded continuously. Both assessments were performed during spontaneous breathing and during 6 cycles/min controlled ventilation in random order. The depressor and bradycardic responses to neck suction were significantly larger during slow breathing than in spontaneous breathing (+32 and +85%, respectively; both P < 0.01). The alpha index was also significantly larger during slow breathing (+62%; P < 0.01). Even after the volunteers were divided into older (> 50 years, n = 9) and younger (< 30 years, n = 9) groups, the baroreflex potentiation related to slow breathing was clearcut and significant for both the depressor (+46 and +24% older and younger volunteers; both P < 0.01) and the bradycardic (+130 and +73% older and younger volunteers; both P < 0.01) responses. When the assessment was made by computing the cross-spectral alpha index, a marked potentiation related to slow breathing was observed in younger volunteers (+99%; P < 0.01), whereas in older volunteers only a trend to an enhancement (by 32%; P < 0.055) was observed. Slow controlled breathing is associated with potentiation of both the depressor and the cardio-inhibitory components of the arterial baroreflex, the potentiation being largely similar regardless of the age of the individual.

Baroreceptor control of heart rate in the awake toad: peripheral autonomic effectors and arterial baroreceptor areas

Systemic injection of sodium nitroprusside (30 μg/kg, i.v.) in the awake Bufo paracnemis toad induced a fall in arterial blood pressure and tachycardia. This tachycardia, but not the hypotension, was significantly reduced in toads with bilateral electrolytic lesion of the caudal and commissural regions of the solitary tract nucleus and in animals with transection of the spinal cord, 2 mm below the obex. This indicates that the tachycardia is reflex, depends on the integrity of the solitary tract nucleus and is due to descending spinal autonomic activation. Pretreatment with propranolol (4 mg/kg, i.v.) significantly reduced the tachycardia but did not block it completely, showing the importance of beta-adrenoceptors in its genesis. The reflex increase in heart rate induced by nitroprusside was not statistically significant in animals with bilateral section of the laryngeal nerve, whose baroreceptor fibers originate from the pulmocutaneous artery or in animals in which the bilateral section of the laryngeal nerve was performed together with section of the glossopharyngeal nerves, which incorporate fibers originating from the carotid labyrinth. The reduction of the reflex tachycardia was significant in toads with aortic arch denervation alone or combined with section of the laryngeal nerves or in animals with complete denervation of the three baroreceptors areas. These results suggest that the region of the aortic arch, when submitted to unloading, is the most important baroreceptor zone for cardiac compensation in toads.

Baroreflex control of heart rate in a canine model of obstructive sleep apnea.

We have recently demonstrated the development of systemic hypertension in a canine model of obstructive sleep apnea (OSA), but the underlying physiological mechanisms were not identified. Therefore, the purpose of this study was to examine the effect of OSA on arterial baroreceptor control of heart rate (HR) in this canine model. OSA was produced in three dogs for 1 to 3 mo. Baroreflex control of HR was determined with graded infusions of vasoactive agents (phenylephrine and nitroprusside) administered over 30 to 60 s, during which steady-state systolic blood pressure (BP) and cardiac R-R interval responses were recorded. BP was measured with a permanently implanted arterial catheter and a telemetry system. Although, as previously reported, OSA resulted in increases in daytime (awake) mean BP of 6.0 to 26.8 mm Hg, there was no change in daytime baseline HR or in the slope of the systolic BP-R-R interval curve (p > 0.2). The findings demonstrate that OSA in the dog is associated with resetting of the baroreceptors to a higher pressure, but no change in baroreflex sensitivity.

Baroreflex Sensitivity

BackgroundArterial baroreceptors play a central role in governing autonomic outflow to the heart and are involved in the electrophysiological mechanisms by which sympathetic activation may initiate a ventricular tachyarrhythmia and vagal activation may have antifibrillatory effects. Stimulation of arterial baroreceptors results in sympathoinhibition and efferent vagal activation. Cardiovascular disease may alter baroreceptor function leading to inappropriate or excessive autonomic activity in response to blood pressure changes.MethodsEvidence obtained in an experimental preparation in chronically infarcted dogs opened the way to the understanding of the importance of the analysis of baroreceptor control of heart rate in risk stratification. Among several methodologies, the measurement of the reflex R‐R interval lengthening following a blood pressure rise induced by bolus injections of phenylephrine has been shown to provide clinically relevant information as a measure of the capability to augment vagal activity.ResultsFollowing pilot studies conducted by different groups of investigators, the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) trial in a series of 1284 myocardial infarction patients has demonstrated that the prognostic value of baroreflex sensitivity is largely independent from the established clinical predictors such as left ventricular ejection fraction and ventricular arrhythmias.ConclusionsIn these patients, the value of the information obtained by the combination between left ventricular function and baroreflex sensitivity suggests that this analysis should be included in the risk stratification strategy for identification of patients who may need an implantable automatic defibrillator for primary prevention of sudden cardiac death. The analysis of baroreceptor reflexes is of prognostic value also in patients with chronic heart failure.

Arterial baroreflex impairment in patients during acute coronary occlusion.

We tested whether acute coronary occlusion interferes with arterial baroreceptor control of heart rate in humans. Subnormal baroreflex sensitivity (BRS) is an important risk indicator for sudden death. Animal research indicates that both chronic myocardial infarction and acute coronary occlusion impair baroreflex modulation of heart rate. We measured RR interval prolongation after phenylephrine-induced systolic pressure increases before and during 2-min coronary occlusions in 47 patients (27 men) undergoing clinically indicated single-vessel coronary angioplasty for stenoses in the proximal or midportion of the vessel causing >50% reduction in the arterial diameter, with normal antegrade flow (33 anterior descending, 10 circumflex, 4 right coronary artery). A control group of 11 patients treated for chronic total occlusion of a coronary artery was assessed to evaluate nonspecific changes in baroreflex function during a 2-min balloon inflation in the occluded artery. The BRS decreased from 5.2+/-3.8 (mean+/-SD) to 4.1+/-3.5 ms x mm Hg(-1) (p=0.01) during the coronary occlusion in the 28 patients with preserved arterial baroreceptor control of heart rate-that is, adequate blood pressure responses and correlation coefficients of the slopes both in baseline and during coronary occlusion. The same phenylephrine dose increased systolic pressure less during than before coronary artery occlusion (21+/-21 versus 36+/-16 mm Hg, p < 0.0001), and in 6 patients it failed to prevent systolic pressure reduction during occlusion. Correlation coefficients of the baroreflex regressions decreased from 0.81+/-0.27 to 0.47+/-0.44 (p < 0.0001) during coronary artery occlusion in the 41 patients with adequate systolic pressure rises in both phenylephrine tests, and the association between RR intervals and rising systolic pressures was lost in 13 patients during coronary occlusion. Balloon inflation in a chronic total occlusion of a coronary artery did not cause significant changes in BRS (from 5.3+/-4.0 to 5.2+/-3.7 ms x mm Hg(-1)), correlation coefficient of the slope or phenylephrine-induced pressure rise. Our study shows that abrupt coronary occlusion impairs baroreflex modulation of vagal and sympathetic nervous outflow in humans.

Baroreflex control of sympathetic nerve activity in essential and secondary hypertension.

Studies performed in experimental animals and in humans have documented that high blood pressure markedly impairs baroreceptor control of heart rate. Whether a similar impairment also characterizes baroreceptor control of sympathetic activity modulating peripheral vasomotor tone is still unknown. In 28 untreated essential hypertensive subjects [14 of moderate and 14 of more severe degree, age 51.6+/-2.4 and 52.6+/-2.1 years (mean+/-SEM)] and in 13 untreated secondary hypertensives (renovascular or pheochromocytoma, age 50.1+/-4.6 years), we measured beat-to-beat arterial blood pressure (finger photoplethysmographic device), heart rate (electrocardiogram), and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Data were compared with those obtained in 15 age-matched normotensive control subjects. Muscle sympathetic nerve activity (bursts per 100 heart beats) showed a progressive and significant (P<.01) increase from normotension (40.3+/-3.3) to moderate (55.6+/-4.1) and more severe essential hypertension (68.2+/-4.1), paralleling the progressive increase in blood pressure values. In contrast, muscle sympathetic nerve activity was not increased in secondary hypertensives (40.5+/-6.7) despite blood pressure values similar to or even greater than those of severe essential hypertensives. In both essential and secondary hypertensives, baroreceptor-heart rate control was displaced toward elevated blood pressure values and markedly impaired compared with normotensive subjects (average reduction, 38.5%). In contrast, the sympathoinhibitory and sympathoexcitatory responses to baroreceptor stimulation and deactivation were displaced toward elevated blood pressure values but similar in all groups. Thus, sympathetic activation characterizes essential but not secondary hypertension. Regardless of its nature, however, hypertension is not accompanied by an impairment of baroreceptor modulation of sympathetic activity.

Baroreflex sensitivity assessed by complex demodulation of cardiovascular variability.

We used complex demodulation of cardiac interval and systolic arterial blood pressure oscillations in the low-frequency band (0.04 to 0.14 Hz) to investigate baroreceptor control of heart rate. Baroreflex sensitivity was defined as the instantaneous amplitude of complex-demodulated oscillations in the RR interval divided by the instantaneous amplitude of complex-demodulated oscillations in systolic blood pressure. We evaluated the method using both simulated and actual data obtained from 33 healthy nonsmokers during supine and standing postures. To test the validity and reliability of the method, we compared the mean values of baroreflex sensitivity calculated using complex demodulation with the values obtained using power spectral analysis and sequential analysis of spontaneous variations in blood pressure and RR interval. All three methods applied to the simulated data yielded the same values of baroreceptor sensitivity. Mean values of baroreflex sensitivity assessed by complex demodulation of the actual data were similar to those calculated by both power spectral analysis and sequential analysis (13.9 +/- 5.2 versus 13.7 +/- 6.7 or 14.3 +/- 6.5 ms/mm Hg for supine and 7.3 +/- 2.8 versus 7.0 +/- 3.0 or 7.2 +/- 2.8 ms/mm Hg for standing, respectively). In addition, a significant correlation existed between the values obtained by complex demodulation and power spectral analysis (r = .97, P = .0001) and sequential analysis (r = .98, P = .0001). Furthermore, complex demodulation-derived baroreflex sensitivity fluctuated across time during both the supine and standing postures, and this could not be discerned by power spectral analysis. The results indicate that complex demodulation provides a dynamic assessment of baroreflex sensitivity and may be a useful tool in exploring reflex autonomic control of the cardiovascular system.

Cardiovascular effects produced by bradykinin microinjection into the nucleus tractus solitarii of anesthetized rats

In this study, we characterized the cardiovascular effects produced by microinjection of doses in the femtomole range of bradykinin (BK) into the nucleus tractus solitarii of male Wistar rats (230–280 g, n = 120) anesthetized with urethane (1.2 g/kg, i.p.). Microinjections of BK (1, 10, 100 fmol, and 1 and 10 pmol, in 50 nl) or vehicle (NaCl, 0.9%) were made by using a triple-barreled glass micropipette into the medial nTS (0.4 mm anterior, 0.3 mm lateral to the obex and 0.3 mm deep from the dorsal surface). Microinjection of BK produced a shallow dose-dependent decrease in mean arterial pressure and heart rate reaching −18 ± 6 mmHg and −21 ± 5 beats/min, with the dose of 10 pmol. The peripheral mechanism of these effects, tested in animals treated with methylatropine (2 mg/kg, i.V.), or propranolol (2 mg/kg, i.v.) or prazosin (30 μg/kg, i.v.), was shown to be mainly dependent on an increase in vagal efferent activity for bradycardia and a decrease in sympathetic activity for hypotension. In order to investigate the receptor subtype involved in these effects, BK was microinjected into the nTS before and after the injection of the B 1 receptor antagonist, Des-Arg 9-Leu 8-BK (DALBK) (11.5 pmol) or before and after the B 2 receptor antagonist, HOE-140 (7.7 pmol). The cardiovascular effects of BK were significantly attenuated by the microinjection of HOE-140 and DALBK into the nTS. The effect of BK microinjected into the nTS on the baroreflex modulation was also investigated. While BK produced a significant facilitation of the baroreflex, HOE-140 and DALBK produced a significant attenuation of the baroreceptor control of heart rate. Taken together, the data presented in this study indicate the nTS as a site, in the central nervous system, for the modulatory effect of BK on the central cardiovascular control.

Effects of aging on 24-h dynamic baroreceptor control of heart rate in ambulant subjects

The effects of aging on the dynamic modulation of baroreflex sensitivity over 24 h was assessed in eight elderly (mean age +/- SD, 63.9 +/- 3.2 yr) and in eight young (23.9 +/- 6.1 yr) mild or moderate essential hypertensive patients, who were subject to a 24-h intra-arterial (Oxford technique) blood pressure recording in ambulatory conditions. The sensitivity of baroreflex control of the heart rate was dynamically assessed by quantifying 1) the slope of the regression line between pulse interval (the reciprocal of heart rate) and systolic blood pressure changes over spontaneously occurring hypertension-bradycardia or hypotension-tachycardia sequences (time domain analysis) and 2) the ratio between spectral-powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha-coefficient: frequency domain analysis). The 24-h average sequence slope was lower in old than in young individuals (4.4 +/- 0.5 vs. 9.9 +/- 1.3 and 4.8 +/- 0.7 vs. 8.4 +/- 1.4 ms/mmHg for hypertension-bradycardia and hypotension-tachycardia sequences, respectively; P < 0.05 for both). Similar results were obtained by using the alpha-coefficient approach. The marked nighttime increase in baroreflex sensitivity observed in young individuals was much less evident in the elderly. Thus 24-h baroreflex sensitivity is markedly impaired by aging. The impairment becomes manifest also as an inability to increase baroreflex sensitivity at night.

Early disturbance of baroreflex control of heart rate after tail suspension in conscious rats.

Experiments were performed on conscious chronically instrumented rats maintained on tail suspension to determine the time course of changes in baroreceptor control of heart rate produced by this procedure. Pressor responses were elicited by bolus injections of graded doses of phenylephrine and sodium nitroprusside, permitting evaluation of the totality of the sigmoidal curve relating mean arterial pressure to heart rate. Compared with control rats maintained at 0 degrees, rats maintained at 20 degrees using tail suspension for 24 h showed a significant reduction in reflex gain (-3.9 +/- 0.1 vs. -5.8 +/- 0.3 beats/min; P < 0.001) together with a reduction in the upper (472 +/- 11 vs. 512 +/- 5 beats/min; P < 0.01) and lower (270 +/- 3 vs. 284 +/- 2 beats/min; P < 0.01) plateaus of the sigmoidal curve. In three groups of rats, the sigmoidal curve was studied successively after returning for 1, 24, and 48 h at 0 degrees. The observed change in the gain of the reflex returned toward control values after 48 h, whereas the other parameters characterizing the sigmoidal curve did not change significantly. Transient but significant modifications of heart rate (tachycardic response) after the immediate return to the horizontal position were observed. The study provides evidence that 1) a significant change of the totality of the sigmoidal curve characterizing baroreceptor control of heart rate occurs very early after tail suspension in rats and 2) the gain of the reflex is restored during the 48 h after release of tail suspension, whereas the other parameters characterizing the curve, particularly the plateaus, remain altered.

Differential baroreceptor reflex modulation by centrally infused angiotensin peptides.

The present study was designed to investigate the effect of intracerebroventricular (icv) and intravenous (iv) infusion of angiotensin (ANG)-(1-7), ANG III, and ANG II on the baroreceptor control of heart rate (BHR) in conscious rats. Reflex changes in HR were elicited by bolus iv injection of either phenylephrine or sodium nitroprusside before and within 1 and 3 h of icv infusion of ANG II (n = 10), ANG III (n = 9), ANG-(1-7) (n = 9), or saline (n = 9) at a rate of 3 nmol.7.5 microliter-1.h-1. In another group of animals (n = 23), iv infusion of the same amount of ANG peptides was carried out at a rate of 0.7 ml/h. The average ratio of changes in HR in beats per minute and changes in mean arterial pressure (MAP, mmHg) was used as an index of BHR sensitivity. ANG II and ANG III produced a significant increase in the basal levels of MAP, but only during the first hour of infusion (iv or icv). No significant changes in baseline HR were observed. ANG-(1-7) and saline infusion did not change basal levels of HR or MAP (iv or icv). ANG II (iv and icv) and ANG III (icv) caused a significant decrease in the BHR sensitivity for reflex bradycardia. In contrast, icv infusion of ANG-(1-7) induced a significant increase in BHR sensitivity for reflex bradycardia (-3.0 +/- 0.3, 1 h, and -2.8 +/- 0.1 beats.min-1.mmHg-1, 3 h vs. -2.1 +/- 0.2 beats.min-1.mmHg-1, before infusion).(ABSTRACT TRUNCATED AT 250 WORDS)

Centrally infused bradykinin increases baroreceptor reflex sensitivity.

Kinins are present in the central nervous system, and central administration of bradykinin increases blood pressure and heart rate. In this study, we determined the effect of intracerebroventricular infusion of bradykinin on the baroreceptor reflex of conscious rats. Male Wistar rats were anesthetized with thiobarbital (40 mg/kg i.p.), and chronic intracerebroventricular cannulas (25 gauge) were implanted into the lateral ventricles. Baroreceptor control of heart rate was evaluated by recording reflex heart rate changes (beats per minute) in response to mean arterial pressure changes (mm Hg) produced by bolus injection of phenylephrine (0.5-20 micrograms/kg i.v.) or sodium nitroprusside (0.5-25 micrograms/kg i.v.). The ratio beats per minute/mm Hg or the mean slope of the individual regression lines of the relation between heart rate and mean arterial pressure changes for increases or decreases in arterial pressure was used as an index of baroreceptor reflex sensitivity. Baroreceptor control of heart rate was evaluated within 1 and 3 hours of intracerebroventricular infusion of bradykinin (7.5 micrograms/7 microliters/hr) or saline (7 microliters/hr). There was no change in basal mean arterial pressure or heart rate during central bradykinin infusion (112 +/- 2 mm Hg and 402 +/- 18 beats per minute in the control period). After 1 hour of central bradykinin infusion, there was a significant increase of baroreceptor reflex sensitivity for increments in mean arterial pressure (-2.91 +/- 0.26 versus -1.5 +/- 0.24 beats per minute/mm Hg in the control period; p less than 0.01, paired Student's t test). In contrast, no significant changes were observed for the reflex tachycardia. Similar results were obtained with 3 hours of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of aging on the heart rate and blood pressure influences of arterial baroreceptors in awake rats.

The effect of aging on arterial baroreceptor control of heart rate and blood pressure was evaluated in unanesthetized normotensive rats aged 5-6 (young), 12-16 (adult) and 75-90 (old) weeks. Each rat was chronically implanted with arterial and venous femoral catheters and with bilateral balloon-in-cuff occluders around the common carotid arteries. Baroreceptor control of heart rate was assessed by the bradycardic and tachycardic response to intravenous boluses of phenylephrine and nitroprusside, respectively. Carotid baroreceptor control of blood pressure was assessed by a 12-s bilateral common carotid occlusion (CCO). All baroreflex responses were similar in young and adult rats. Compared with the young group, old rats showed a marked reduction of the bradycardic and tachycardic baroreflex response (-42% and -46%, respectively, P less than 0.05). The initial pressor responses to CCO were also impaired in the old animals (3 s: -63%, 6 s: -54%; both P less than 0.01), whereas the peak pressor response (9 and 12 s) was virtually identical in the young and old groups. The preservation of the peak pressor response to CCO in old rats was independent of chemoreceptor activation, aortic baroreceptors or cerebral ischemia. Thus, aging impairs baroreceptor control of heart rate but alters baroreceptor control of blood pressure, as assessed by the pressor response to CCO, only in its fast-developing component, leaving its longer-term component unaffected.

Reflex control of circulation in the elderly

Baroreceptor control of heart rate is markedly reduced in elderly subjects. However, the effects of aging on baroreceptor control of blood pressure and on the vascular and neurohumoral influences of volume cardiopulmonary receptors are unknown. In this paper we report evidence that in both conscious rats and humans aging is associated with a fall in the baroreceptor ability to rapidly cause blood pressure changes, but that the more long-term carotid baroreceptor control of blood pressure remains similar to that observed in younger individuals. Early and late cardiopulmonary receptor modulation of vascular resistance is impaired by aging, which also reduces the influence of this reflex on renin secretion. These dynamic and steady-state alterations in reflex cardiovascular control account for several hemodynamic abnormalities of the advanced age.

EFFECTS OF HALOTHANE, KETAMINE, PROPOFOL AND ALFENTANIL ANAESTHESIA ON CIRCULATORY CONTROL IN RABBITS

1. We have made a within-rabbit comparison of the effects of four general anaesthetic regimens on the haemodynamic response to acute reduction in central blood volume and on baroreflex control of heart rate. 2. Acute haemorrhage was simulated by gradually inflating a cuff on the inferior vena cava in order to cause cardiac output to fall at a constant rate of 8.5%/min while the responses of systemic vascular resistance, arterial pressure and heart rate were measured. The full range of the baroreceptor-heart rate reflex was elicited by inflating aortic and vena caval cuffs. These indices of circulatory control were repeatedly measured within five protocols, to which each rabbit was exposed in randomized order. 3. In each protocol the rabbit was first studied unanaesthetized. Then a small dose of thiopentone sodium was given (16 mg/kg). In the four main protocols the rabbit was then intubated and ventilated, first with 100% oxygen and then with 50% nitrous oxide, during administration of one of four anaesthetic agents. These were halothane (2.0 and 2.5%), ketamine (2.5 mg/kg per min), propofol (0.83 and 1.25 mg/kg per min) and alfentanil (2.5 and 3.33 micrograms/kg per min). In a sham protocol the effects of 100% oxygen, then those of 50 and 75% nitrous oxide, were studied while the rabbit remained conscious. 4. In unanaesthetized rabbits, in the presence or absence of nitrous oxide, the normal biphasic haemodynamic response to simulated haemorrhage occurred. The first, vasoconstrictor, phase was attenuated by halothane, ketamine and propofol, so that arterial pressure fell more steeply than normal. Not only was the vasoconstrictor phase unaffected by alfentanil but it was extended, so that arterial pressure remained at a normal level even when cardiac output had fallen by 59%. This effect of alfentanil appeared to be mediated centrally, since it could be reproduced by injecting small doses (1.5-7.5 micrograms) into the fourth ventricle. All four anaesthetic agents and nitrous oxide attenuated the baroreceptor control of heart rate. The effect was least with nitrous oxide and alfentanil, greatest with halothane.