Changes In Baroreflex Function Research Articles

Baroreflex responses to limb venous distension in humans.

The venous distension reflex (VDR) is a pressor response evoked by peripheral venous distension and accompanied by increased muscle sympathetic nerve activity (MSNA). The effects of venous distension on the baroreflex, an important modulator of blood pressure (BP), have not been examined. The purpose of this study was to examine the effect of the VDR on baroreflex sensitivity (BRS). We hypothesized that the VDR will increase the sympathetic BRS (SBRS). Beat-by-beat heart rate (HR), BP, and MSNA were recorded in 16 female and 19 male young healthy subjects. To induce venous distension, normal saline equivalent to 5% of the forearm volume was infused into the veins of the occluded forearm. SBRS was assessed from the relationship between diastolic BP and MSNA during spontaneous BP variations. Cardiovagal BRS (CBRS) was assessed with the sequence technique. Venous distension evoked significant increases in BP and MSNA. Compared with baseline, during the maximal VDR response period, SBRS was significantly increased (-3.1 ± 1.5 to -4.5 ± 1.6 bursts·100 heartbeats-1·mmHg-1, P < 0.01) and CBRS was significantly decreased (16.6 ± 5.4 to 13.8 ± 6.1 ms·mmHg-1, P < 0.01). No sex differences were observed in the effect of the VDR on SBRS or CBRS. These results indicate that in addition to its pressor effect, the VDR altered both SBRS and CBRS. We speculate that these changes in baroreflex function contribute to the modulation of MSNA and BP during limb venous distension.

Short-term water deprivation does not increase blood pressure variability or impair neurovascular function in healthy young adults.

High dietary salt increases arterial blood pressure variability (BPV) in salt-resistant, normotensive rodents and is thought to result from elevated plasma [Na+] sensitizing central sympathetic networks. Our purpose was to test the hypothesis that water deprivation (WD)-induced elevations in serum [Na+] augment BPV via changes in baroreflex function and sympathetic vascular transduction in humans. In a randomized crossover fashion, 35 adults [17 female/18 male, age: 25 ± 4 yr, systolic/diastolic blood pressure (BP): 107 ± 11/60 ± 7 mmHg, body mass index: 23 ± 3 kg/m2] completed two hydration protocols: a euhydration control condition (CON) and a stepwise reduction in water intake over 3 days, concluding with 16 h of WD. We assessed blood and urine electrolyte concentrations and osmolality, resting muscle sympathetic nerve activity (MSNA; peroneal microneurography; 18 paired recordings), beat-to-beat BP (photoplethysmography), common femoral artery blood flow (Doppler ultrasound), and heart rate (single-lead ECG). A subset of participants (n = 25) underwent ambulatory BP monitoring during day 3 of each protocol. We calculated average real variability as an index of BPV. WD increased serum [Na+] (141.0 ± 2.3 vs. 142.1 ± 1.7 mmol/L, P < 0.01) and plasma osmolality (288 ± 4 vs. 292 ± 5 mosmol/kg H2O, P < 0.01). However, WD did not increase beat-to-beat (1.9 ± 0.4 vs. 1.8 ± 0.4 mmHg, P = 0.24) or ambulatory daytime (9.6 ± 2.1 vs. 9.4 ± 3.3 mmHg, P = 0.76) systolic BPV. Additionally, sympathetic baroreflex sensitivity (P = 0.20) and sympathetic vascular transduction were not different after WD (P = 0.17 for peak Δmean BP following spontaneous MSNA bursts). These findings suggest that, despite modestly increasing serum [Na+], WD does not affect BPV, arterial baroreflex function, or sympathetic vascular transduction in healthy young adults.

Aortic Depressor Response is Blunted Following Ovariectomy: Evidence for Involvement of Central but not Peripheral Afferent Pathways in Rat

Sex differences in aortic baroreflex (BRx) function are well documented. In female rats, selective electrical stimulation of myelinated aortic baroreceptor fibers evokes a much greater reduction in blood pressure and heart rate than in age‐matched males. Our lab has a longstanding interest in the electrophysiological properties of vagal neurons that give rise to these sexually dimorphic barosensory fibers. We have previously shown that myelinated “Ah‐type” afferent neurons lose their capacity for sustained repetitive discharge after ovariectomy (OVX). Furthermore, 4 or more weeks after OVX the enhanced BRx response of female rats is blunted. This longitudinal study aims to quantify the transition in BRx dynamics over the first 4 weeks after OVX. Age‐matched cohorts of normal (OVI, n = 11) and OVX rats (n = 26) were prepared for bipolar electrical stimulation of aortic depressor nerve. Rats at 1 week post OVX were not significantly different than OVI controls. However, rats that were 2 to 4 weeks post OVX exhibited blunted depressor responses that were 3 – 4 times smaller than OVI. To determine whether Ah‐type afferent fiber conduction was being compromised, we measured electrically evoked compound action potentials (CAP) from additional cohorts of OVI (n = 10) and OVX rats (n = 15) at 2, 3 and 4 weeks after OVX. These studies revealed no significant changes in the recruitment profile of Ah myelinated fibers nor the integrated electrical energy of the CAP. Interestingly, at 4 or more weeks following OVX the CAP showed evidence of temporal dispersion. Collectively, our results suggest that the onset of early changes in BRx function after OVX are likely driven by central mechanisms as the evoked conduction profile of Ah barosensory fibers appears unaltered.

Beneficial effects of physical activity on baroreflex control in the elderly.

The baroreflex mechanisms, by controlling autonomic outflow to the heart and circulation, contribute importantly to neural circulatory control. The main function of the baroreflex is to prevent wide fluctuations in arterial blood pressure and to maintain the physiological homeostasis under basal resting conditions and in response to acute stress. Baroreflex-mediated changes in autonomic outflow affect heart rate, myocardial contractility, and peripheral vascular resistance. The baroreflex control of heart rate is of particular interest in pathological conditions, since it has been associated with increased propensity for cardiac mortality and sudden death. Aging is associated with significant cardiovascular modifications. The changes in baroreflex function that occur with age have been systematically studied by several methodological approaches. The available evidence indicates a reduced arterial baroreflex control of heart rate favoring an increase in sympathetic and a decrease in parasympathetic drive to the heart as well as an impairment in the baroreceptor control of blood pressure. Both kinds of changes have resultant clinical implications. Exercise training can modulate the age-related decline in baroreflex function and the attending abnormalities in autonomic control, thus accounting for some of the beneficial effects of physical activity in reducing the risk of cardiovascular morbidity and mortality.

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Translational Examination of Changes in Baroreflex Function After Renal Denervation in Hypertensive Rats and Humans

Renal denervation has shown promise in the treatment of resistant hypertension, although the mechanisms underlying the blood pressure (BP) reduction remain unclear. In a translational study of spontaneously hypertensive rats (n=7, surgical denervation) and resistant hypertensive human patients (n=8; 5 men, 33-71 years), we examined the relationship among changes in BP, sympathetic nerve activity, and cardiac and sympathetic baroreflex function after renal denervation. In humans, mean systolic BP (SBP; sphygmomanometry) and muscle sympathetic nerve activity (microneurography) were unchanged at 1 and 6 months after renal denervation (P<0.05). Interestingly, 4 of 8 patients showed a 10% decrease in SBP at 6 months, but sympathetic activity did not necessarily change in parallel with SBP. In contrast, all rats showed significant and immediate decreases in telemetric SBP and lumbar sympathetic activity (P<0.05), 7 days after denervation. Despite no change in SBP, human cardiac and sympathetic baroreflex function (sequence and threshold techniques) showed improvements at 1 and 6 months after denervation, particularly through increased sympathetic baroreflex sensitivity to falling BP. This was mirrored in spontaneously hypertensive rats; cardiac and sympathetic baroreflex sensitivity (spontaneous sequence and the Oxford technique) improved 7 days after denervation. The more consistent results in rats may be because of a more complete (>90% reduction in renal norepinephrine content) denervation. We conclude that (1) renal denervation improves BP in some patients, but sympathetic activity does not always change in parallel, and (2) baroreflex sensitivity is consistently improved in animals and humans, even when SBP has not decreased. Determining procedural success will be crucial in advancing this treatment modality.

Heart rate–mediated blood pressure control in preterm fetal sheep under normal and hypoxic–ischemic conditions

The understanding of hypoxemia-induced changes in baroreflex function is limited and may be studied in a fetal sheep experiment before, during, and after standardized hypoxic conditions. Preterm fetal lambs were instrumented at 102 d gestation (term: 146 d). At 106 d, intrauterine hypoxia--ischemia was induced by 25 min of umbilical cord occlusion (UCO). Baroreflex-related fluctuations were calculated at 30-min intervals during the first week after UCO by transfer function (cross-spectral) analysis between systolic blood pressure (SBP) and R-R interval fluctuations, estimated in the low-frequency (LF, 0.04-0.15 Hz) band. LF transfer gain (baroreflex sensitivity) and delay (s) reflect the baroreflex function. Baseline did not differ in LF transfer gain and delay between controls and the UCO group. In controls, LF gain showed postnatal increase. By contrast, LF gain gradually decreased in the UCO group, resulting in significantly lower values 4-7 d after UCO. In the UCO group, LF delay increased and differed significantly from controls. Our results show that intrauterine hypoxia-ischemia results in reduced baroreflex sensitivity over a period of 7 d, indicating limited efficacy to buffer BP changes by adapting heart rate. Cardiovascular dysregulation may augment already present cerebral damage after systemic hypoxia-ischemia in the reperfusion period.

Baroreflex Function in Females: Changes With the Reproductive Cycle and Pregnancy

This review briefly describes the changes in baroreflex function that occur during female reproductive life, specifically during the reproductive cycle and pregnancy. The sensitivity or gain of baroreflex control of heart rate and sympathetic activity fluctuates during the reproductive cycle, reaching a peak when gonadal hormone levels increase, during the follicular phase in women and proestrus in rats. The increase in baroreflex sensitivity (BRS) is likely mediated by estrogen because ovariectomy in rats eliminates the BRS increase, the cyclic profile of changes in BRS mirror the changes in estrogen, and estrogen acts in the brainstem to increase BRS. In contrast, pregnancy depresses both BRS and the maximal level of sympathetic activity and heart rate evoked by severe hypotension. The decrease in BRS may be mediated by a reduction in the actions of insulin in the arcuate nucleus to support the baroreflex. In addition, increased levels of the neurosteroid progesterone metabolite 3α-OH-DHP act downstream in the rostral ventrolateral medulla to suppress maximal baroreflex increases in sympathetic activity. Consequently, these changes in baroreflex function impair blood pressure regulation in the presence of hypotensive challenges such as orthostasis and hemorrhage, a common event during delivery. As a result, peripartum hemorrhage is a major cause of human maternal death.

Baroreflex control of muscle sympathetic nerve activity as a mechanism for persistent sympathoexcitation following acute hypoxia in humans

This study tested the hypothesis that acute isocapnic hypoxia results in persistent resetting of the baroreflex to higher levels of muscle sympathetic nerve activity (MSNA), which outlasts the hypoxic stimulus. Cardiorespiratory measures were recorded in humans (26 ± 1 yr; n = 14; 3 women) during baseline, exposure to 20 min of isocapnic hypoxia, and for 5 min following termination of hypoxia. The spontaneous baroreflex threshold technique was used to determine the change in baroreflex function during and following 20 min of isocapnic hypoxia (oxyhemoglobin saturation = 80%). From the spontaneous baroreflex analysis, the linear regression between diastolic blood pressure (DBP) and sympathetic burst occurrence, the T50 (DBP with a 50% likelihood of a burst occurring), and DBP error signal (DBP minus the T50) provide indexes of baroreflex function. MSNA and DBP increased in hypoxia and remained elevated during posthypoxia relative to baseline (P < 0.05). The DBP error signal became progressively less negative (i.e., smaller difference between DBP and T50) in the hypoxia and posthypoxia periods (baseline: -3.9 ± 0.8 mmHg; hypoxia: -1.4 ± 0.6 mmHg; posthypoxia: 0.2 ± 0.6 mmHg; P < 0.05). Hypoxia caused no change in the slope of the baroreflex stimulus-response curve; however, there was a shift toward higher pressures that favored elevations in MSNA, which persisted posthypoxia. Our results indicate that there is a resetting of the baroreflex in hypoxia that outlasts the stimulus and provide further explanation for the complex control of MSNA following acute hypoxia.

Neurosteroid modulation of arterial baroreflex function in the rostral ventrolateral medulla

Through both genomic and nongenomic actions, ovarian hormones and their metabolites have significant effects on the central nervous system to modulate a variety of regulatory systems, including the cardiovascular system. The major metabolite of progesterone, 3α-hydroxy-dihydroprogesterone, is the most potent endogenous positive modulator of GABA A receptors known and central nervous system levels of this progesterone metabolite fluctuate with the ovarian cycle and are elevated in pregnant animals. Pregnancy is associated with attenuated arterial baroreflex sympathoexcitation and increased tonic GABAergic inhibition of the rostral ventrolateral medulla (RVLM) likely contributes. The current experiments were performed to determine if the effects of pregnancy on arterial baroreflex control of renal sympathetic nerve activity could be mimicked by microinjection of the neuroactive progesterone metabolite into the RVLM. Compared to control values, 15 min after microinjection of 3α-hydroxy-dihydroprogesterone into the RVLM ( n = 10), baseline renal sympathetic nerve activity was decreased to 82% of baseline, and the range (157 ± 10 to 131 ± 11%) and maximum nerve activity (164 ± 9 to 136 ± 12%) for the arterial baroreflex curves were decreased. In contrast, microinjection of the inactive isomer, 3β-hydroxy-dihydroprogesterone into the RVLM ( n = 9), had no effect on baseline nerve activity or the arterial baroreflex nerve activity range or maximum. Thus, although multiple mechanisms likely contribute to pregnancy associated changes in baroreflex function, these experiments suggest that increased levels of 3α-hydroxy-dihydroprogesterone in the RVLM might contribute.

Acute intermittent hypoxia in ratin vivoelicits a robust increase in tonic sympathetic nerve activity that is independent of respiratory drive

Acute intermittent hypoxia (AIH) elicits long-term increases in respiratory and sympathetic outflow (long-term facilitation, LTF). It is still unclear whether sympathetic LTF is totally dependent on changes in respiration, even though respiratory drive modulates sympathetic nerve activity (SNA). In urethane-anaesthetized, vagotomized mechanically ventilated Sprague-Dawley rats, we investigated the effect of ten 45 s episodes of 10% O2-90% N(2) on splanchnic sympathetic nerve activity (sSNA) and phrenic nerve activity (PNA). We then tested whether or not hypoxic sympathetic chemoreceptor and baroreceptor reflexes were changed 60 min after AIH. We found that 17 animals manifested a sustained increase of sSNA (+51.2+/-4.7%) 60 min after AIH, but only 10 of these rats also expressed phrenic LTF compared with the time controls (rats not exposed to hypoxia, n=5). Inspiratory triggered averages of integrated sSNA showed respiratory modulation of SNA regardless of whether or not phrenic LTF had developed. The hypoxic chemoreceptor reflex was enhanced by 60 min after the development of AIH (peak change from 76.9+/-13.9 to 159.5+/-24.9%). Finally, sympathetic baroreceptor reflex sensitivity increased after sympathetic LTF was established (Gainmax from 1.79+/-0.18 to 2.60+/-0.28% mmHg1). Our findings indicate that respiratory-sympathetic coupling does contribute to sympathetic LTF, but that an additional tonic increase of sympathetic tone is also present that is independent of the level of PNA. Sympathetic LTF is not linked to the change in baroreflex function, since the baroreflex appears to be enhanced rather than impaired, but does play an important role in the enhancement of the hypoxic chemoreflex.

Pregnancy and the endocrine regulation of the baroreceptor reflex.

The purpose of this review is to delineate the general features of endocrine regulation of the baroreceptor reflex, as well as specific contributions during pregnancy. In contrast to the programmed changes in baroreflex function that occur in situations initiated by central command (e.g., exercise or stress), the complex endocrine milieu often associated with physiological and pathophysiological states can influence the central baroreflex neuronal circuitry via multiple sites and mechanisms, thereby producing varied changes in baroreflex function. During pregnancy, baroreflex gain is markedly attenuated, and at least two hormonal mechanisms contribute, each at different brain sites: increased levels of the neurosteroid 3alpha-hydroxy-dihydroprogesterone (3alpha-OH-DHP), acting in the rostral ventrolateral medulla (RVLM), and reduced actions of insulin in the forebrain. 3alpha-OH-DHP appears to potentiate baroreflex-independent GABAergic inhibition of premotor neurons in the RVLM, which decreases the range of sympathetic nerve activity that can be elicited by changes in arterial pressure. In contrast, reductions in the levels or actions of insulin in the brain blunt baroreflex efferent responses to increments or decrements in arterial pressure. Although plasma levels of angiotensin II are increased in pregnancy, this is not responsible for the reduction in baroreflex gain, although it may contribute to the increased level of sympathetic nerve activity in this condition. How these different hormonal effects are integrated within the brain, as well as possible interactions with additional potential neuromodulators that influence baroreflex function during pregnancy and other physiological and pathophysiological states, remains to be clearly delineated.

The Valsalva maneuver: screening for drug-induced baroreflex dysfunction

Many drugs can interfere with baroreflex mechanisms thereby impairing blood pressure control, but few have undergone sufficient testing. The state of affairs may be explained by the lack of simple and inexpensive screening tests. In eleven healthy men, we tested the hypothesis that a simple Valsalva maneuver could detect drug-induced changes in baroreflex function that have previously been described using more elaborate and invasive methodologies. They performed Valsalva maneuvers after selective pharmacological inhibition of the norepinephrine transporter (NET) in a placebo-controlled, double-blind, randomized, crossover fashion. Patients with severe autonomic failure served as positive controls. NET inhibition profoundly augmented the blood pressure decrease during phase II and attenuated the blood pressure overshoot in phase IV compared with placebo. Furthermore, NET inhibition increased the heart rate response during the Valsalva maneuver. The Valsalva maneuver recapitulated complex alterations in baroreflex regulation during NET inhibition. Thus, this simple and inexpensive test could be employed as a screening tool for drug-induced baroreflex dysfunction.

Effect of aging on baroreflex function in humans

Arterial blood pressure (BP) is regulated via the interaction of various local, humoral, and neural factors. In humans, the major neural pathway for acute BP regulation involves the baroreflexes. In response to baroreceptor activation/deactivation, as occurs during transient changes in BP, key determinants of BP, such as cardiac period/heart rate (via the sympathetic and parasympathetic nervous system) and vascular resistance (via the sympathetic nervous system), are modified to maintain BP homeostasis. In this review, the effects of aging on both the parasympathetic and sympathetic arms of the baroreflex are discussed. Aging is associated with decreased cardiovagal baroreflex sensitivity (i.e., blunted reflex changes in R-R interval in response to a change in BP). Mechanisms underlying this decrease may involve factors such as increased levels of oxidative stress, vascular stiffening, and decreased cardiac cholinergic responsiveness with age. Consequences of cardiovagal baroreflex impairment may include increased levels of BP variability, an impaired ability to respond to acute challenges to the maintenance of BP, and increased risk of sudden cardiac death. In contrast, baroreflex control of sympathetic outflow is not impaired with age. Collectively, changes in baroreflex function with age are associated with an impaired ability of the organism to buffer changes in BP. This is evidenced by the reduced potentiation of the pressor response to bolus infusion of a pressor drug after compared to before systemic ganglionic blockade in older compared with young adults.

Daytime variability of baroreflex function in patients with obstructive sleep apnoea: implications for hypertension

Obstructive events during sleep in patients with obstructive sleep apnoea (OSA) cause large alterations in blood pressure, and this may lead to changes in baroreflex function with implications for long-term blood pressure control. This study examined the daytime variations in the responses to carotid baroreceptor stimulation in OSA patients. We determined the cardiac and vascular responses every 3 h between 09.00 and 21.00 h in 20 patients with OSA, using graded suctions and pressures applied to a neck collar. These responses were plotted against estimated carotid sinus pressures and, from these plots, baroreflex sensitivities and operating points were taken as the maximal slopes and the corresponding carotid sinus pressures, respectively. We found that at 09.00 h, sensitivity for the control of vascular resistance was at its lowest (--1.2 +/- 0.2% mmHg(-1), compared with --1.9 +/- 0.3% mmHg(-1) at 12.00 h, P < 0.02) and operating point for control of mean arterial pressure was at its highest (101.1 +/- 5.8 mmHg, compared with 94.1 +/- 5.8 mmHg at 12.00 h, P < 0.05). This is in contrast to previous data from normal subjects, in whom sensitivity was highest and operating point lowest at 09.00 h. We suggest that the higher baroreflex sensitivity and lower operating point seen in the mornings in normal subjects may provide a protective mechanism against hypertension and that this protection is absent in patients with OSA. It is possible that the reduced reflex sensitivity and increased operating point in the mornings may actually promote hypertension.

Assessing baroreflex sensitivity by the transfer function method: what are we really measuring?

by governing the autonomic outflow to the heart and blood vessels, arterial baroreceptors play a central role in controlling short-term blood pressure responses to the hemodynamic perturbations continuously occurring in daily life. Abnormalities in baroreflex function are thought to play an

Impaired Baroreceptor Reflex Function of Older ASrAOGEN Rats

Generation of Ang-(1–7) in the dorsal medulla through pathways catalyzed by neprilysin and ACE2 decreases in Sprague-Dawley (SD) rats as they age. Further, we have shown that reduced tissue Ang-(1–7) in aging rats (~70 weeks) contributes to a 40% reduction in baroreceptor reflex control of heart rate associated with increased systolic blood pressure (SBP). On the other hand, transgenic rats with low brain angiotensinogen (ASrAOGEN) do not exhibit increases in SBP as they age. However, data on age-related changes in baroreflex function of ASrAOGEN rats is lacking. Therefore, we assessed baroreflex control of heart rate in Young (3 – 4 months) and Older (15 – 16 months) conscious male ASrAOGEN rats as the slope of the relationship between phenylephrine-induced increases in blood pressure and decreases in heart rate. The heart rate baroreflex was attenuated in Older rats compared to Young rats (1.6 ± 0.6, n = 8 vs 3.6 ± 1.0 msec/mmHg, n = 4, respectively; p< 0.05). Further, heart rate baroreflex sensitivity of older SD rats [0.7 ± 0.2 msec/mmHg (n = 7)] was significantly less than that of older ASrAOGEN rats. Thus, heart rate baroreflex sensitivity declined with age in ASrAOGEN rats but remained higher than that of older SD rats. Since neprilysin and ACE2 mRNAs and Ang-(1–7) forming activity of these enzymes tends to be reduced in medulla oblongata of older ASrAOGEN and SD rats in comparison to that of younger rats, we suggest that decline in local production of Ang-(1–7) contributes to attenuated baroreflex function of ASrAOGEN and SD rats as they age. Support: HL51952; AHA-MA 021515U

Sleep and Hypertension

Even though sleep is widely considered to be a restorative and refreshing process, it is characterized by complex activity of the cardiovascular autonomic mechanisms and by relevant changes of arterial pressure and heart rate. It has been widely reported that fluctuations and variability of cortical and visceral activities involve a differential autonomic regulation of the cardiovascular system in relationship to different sleep cycles. During non–rapid eye movement (REM) sleep, arterial pressure and heart rate tend to decrease, whereas periods of relative hypertension and tachycardia characterize REM periods. With regard to the cardiovascular autonomic modulation, non-REM sleep is characterized by a vagal predominance, whereas during REM sleep, a relative increase in sympathetic activity is demonstrated by an increased sympathetic outflow to muscle blood vessels.1–3 See p 849 Therefore, this continuous cycling of non-REM and REM phases, with the consequent cardiovascular autonomic changes, makes sleep a period of considerable physiological turbulence characterized by sudden and abrupt blood pressure and heart rate changes. This cardiovascular instability has stimulated the investigation of the neural mechanisms involved in maintaining the cardiovascular homeostasis during the different sleep phases. The first pivotal study conducted with the Oxford technique in normotensive and hypertensive subjects4 clearly showed that changes in baroreflex function investigated by quantifying the reflex RR interval lengthening in response to a pharmacologically induced increase in systolic blood pressure (obtained through intravenous injection of phenylephrine), occurred ongoing from wakefulness to sleep. These changes consisted of an increase in the reflex sensitivity and of a resetting, moving the operating point of the reflex toward lower blood pressure values.4 In the past few years, this issue has been further investigated because it is now possible to investigate the arterial baroreflex function by analyzing the correlated blood pressure and spontaneous heart rate …

Effect of chronic stress on the cardiac baroreflex in the post-weanling rat

There is increasing evidence that early life stressors may program blood pressure control mechanisms such that the risk for cardiovascular disease in later life is increased. In the present investigation, the effect of repeated restraint/heat stress during the two-week period immediately after weaning on baroreflex function was determined and the contribution of brain angiotensin II (ANG II) to the changes was assessed in young, conscious, freely moving Sprague Dawley rats. In rats two weeks post weaning, basal MAP was significantly higher and basal HR significantly lower than rats tested immediately after weaning. This change in the operating point of HR was not accompanied by any changes in baroreflex function. Treatment with chronic icv infusion of losartan, an AT1 receptor antagonist, during the two-week period prevented the changes in basal MAP and HR. Chronic stress during the two weeks post weaning, whether due to surgical implantation of icv cannulae or due to restraint/heat stress, significantly shifted the set-point of the baroreflex function to a higher pressure. Chronic icv infusion of losartan during the period prevented these effects (at least in the case of stress due to the presence of icv cannulae) suggesting a role for brain ANG II in the change. Changes in the expression of CRH mRNA in the paraventricular nucleus could not explain the stress-related change in baroreflex function. If the rightward shift in the baroreflex persists into adulthood, it could increase the susceptibility to cardiovascular diseases such as hypertension.

Contribution of central ANG II to acute stress-induced changes in baroreflex function in young rats.

The aim of the present investigation was to characterize the baroreflex in weaned 23- to 25-day-old rats when maternal influences were no longer present. The relationship between mean arterial pressure (MAP) and heart rate (HR) was determined during baroreceptor loading with phenylephrine and baroreceptor unloading with sodium nitroprusside in conscious rats, first in the freely moving state and subsequently during acute stress. In unstressed rats, the slope of the relationship between MAP and HR was greater during baroreceptor loading than baroreceptor unloading. Acute stress significantly attenuated the slope of the response to baroreceptor loading but increased the slope of the response to baroreceptor unloading. Pretreatment with intracerebroventricular or intravenous losartan, an AT(1) receptor antagonist, or intracerebroventricular alpha-helical corticotropin-releasing hormone (alpha-hCRH), a receptor antagonist, before the stress significantly reduced the stress-induced attenuation of slope during baroreceptor loading. Hence, young postweaning rats can alter baroreflex function during acute stress in a manner that would favor increases in MAP. Even at this young age, a central action of ANG II and CRH contributes to these stress-induced adaptations.