Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men

Cardiovagal baroreflex sensitivity (BRS) declines with advancing age in healthy men. We tested the hypothesis that oxidative stress contributes mechanistically to this age-associated reduction. Eight young (23 +/- 1 yrs, means +/- SE) and seven older (63 +/- 3) healthy men were studied. Cardiovagal BRS was assessed using the modified Oxford technique (bolus infusion of 50-100 microg sodium nitroprusside, followed 60 s later by a 100- to 150-microg bolus of phenylephrine hydrochloride) in triplicate at baseline and during acute intravenous ascorbic acid infusion. At baseline, cardiovagal BRS (slope of the linear portion of the R-R interval-systolic blood pressure relation during pharmacological changes in arterial blood pressure) was 56% lower (P < 0.01) in older (8.3 +/- 1.6 ms/mmHg) compared with young (19.0 +/- 3.1 ms/mmHg) men. Ascorbic acid infusion increased plasma concentrations similarly in young (62 +/- 9 vs. 1,249 +/- 72 micromol/l for baseline and during ascorbic acid; P < 0.05) and older men (62 +/- 4 vs. 1,022 +/- 55 micromol/l; P < 0.05) without affecting baseline blood pressure, heart rate, carotid artery compliance, or the magnitude of change in systolic blood pressure in response to bolus sodium nitroprusside and phenylephrine hydrochloride infusion. Ascorbic acid (vitamin C) infusion increased cardiovagal BRS in older (Delta58 +/- 16%; P < 0.01), but not younger (Delta - 4 +/- 4%) men. These data provide experimental support for the concept that oxidative stress contributes mechanistically to age-associated reductions in cardiovagal BRS in healthy men.     

Angiotensin restores atrial natriuretic factor-induced decrease of baroreceptor sensitivity in normotensive rats, but not in spontaneously hypertensive rats

The effect of atrial natriuretic factor (ANF) on baroreflex sensitivity was determined in unanesthetized normotensive (Wistar-Kyoto, WKY) or spontaneously hypertensive rats (SHR) during acute hypertensive stimuli (phenylephrine) or hypotensive stimuli (sodium nitroprusside). The i.v. dose of rat ANF [( Ser99,Tyr126]ANF) was 50 ng/min per rat, sufficient to decrease mean arterial blood pressure (ABP) by about 6 mmHg (1 mmHg = 133.3 Pa) in WKY. SHR showed no change in ABP with this ANF dose. During a control infusion of physiological saline, the mean heart rate (HR) response to increases in ABP was -1.30 +/- 0.27 beats/min (bpm)/mmHg in WKY and -0.37 +/- 0.22 in SHR (p less than 0.05). These values were not affected significantly by ANF. However, ANF blunted chronotropic responses to ABP decreases. The control values of the delta HR/delta ABP slope in WKY and SHR were -2.34 +/- 0.57 and -2.01 +/- 0.37 bpm/mmHg, respectively. In the presence of ANF, the slope changed to -0.36 +/- 0.43 (i.e., bradycardia in response to hypotension) in WKY and to +0.20 +/- 0.21 in SHR (p less than 0.005 for the difference from control for both). This ANF-induced loss of baroreflex sensitivity was reversed in WKY by the addition of angiotensin I (sufficient to increase ABP by 5 mmHg in control rats). Angiotensin did not restore baroreflex sensitivity in ANF-infused SHR, and ANF had no effect on the ABP increase caused by angiotensin in either group. The data suggest that ANF does not act on baroreceptor structures directly, but inhibits mechanisms involved in efferent sympathetic activation. Parasympathetic responses do not appear to be compromised.     

Baroreceptor afferent discharge in the pregnant rat

Pregnancy is associated with blunted reflex responses to cardiac and arterial baroreceptor stimulation. We tested the hypothesis that arterial baroreceptor afferent discharge is attenuated in response to a pressure stimulus in pregnant rats. Multifiber aortic depressor nerve activity (ADNA), mean arterial pressure (MAP), and heart rate were measured in anesthetized (pentobarbital sodium, 35 mg/kg ip) late-pregnant and virgin rats in response to increases ?phenylephrine (PE), 1.5-24 microg. kg(-1). min(-1) and 1-16 microg/kg and decreases ?sodium nitroprusside (SNP), 5-80 microg. kg(-1). min(-1) and 0.05-16 microg/kg in MAP. Resting MAP was lower in pregnant rats, but changes in MAP were similar to those in virgin rats during both PE and SNP administration. ADNA was significantly attenuated in pregnant animals during both PE and SNP infusions (P < 0.05) due to a more rapid adaptation to the pressure stimulus. Bolus drug administration evoked similar changes in MAP and ADNA in both groups; however, the maximum decrease in ADNA was achieved at the lowest dose of SNP in pregnant rats. Thus baroreceptor afferent discharge is attenuated in pregnant rats, and this involves a more rapid adaptation to a pressure stimulus.     

Baroreflex depression persists in the early phase after hypertension reversal

The baroreflex control of heart rate (HR) was evaluated in conscious chronic renal hypertensive rats (RHR; 1K-1C, 2 mo) under control conditions and after reversal of hypertension by unclipping the renal artery or sodium nitroprusside infusion. Unclipping and nitroprusside infusion were both followed by significant decreases in the mean arterial pressure (unclipping: from 199 +/- 4 to 153 +/- 8 mmHg; nitroprusside infusion: from 197 +/- 9 to 166 +/- 6 mmHg) as well as slight and significant increases, respectively, in the baroreflex bradycardic response index (unclipping: from 0.2 +/- 0.04 to 0.6 +/- 0.1 beats x min(-1) x mmHg(-1); nitroprusside infusion: from 0.1 +/- 0.04 to 0.5 +/- 0.1 beats x min(-1) x mmHg(-1)). However, this index was still depressed compared with that for normotensive control rats (2.1 +/- 0.2 beats x min(-1) x mmHg(-1)). The index for the baroreflex tachycardic response was also depressed under control conditions and remained unchanged after hypertension reversal. RHR possessed markedly attenuated vagal tone as demonstrated by pharmacological blockade of parasympathetic and sympathetic control of HR with methylatropine and propranolol, respectively. A reduced bradycardic response was also observed in anesthetized RHR during electrical stimulation of the vagus nerve or methacholine chloride injection, indicating impairment of efferent vagal influence over the HR. Together, these data indicate that 2 h after hypertension reversal in RHR, the previously described normalization of baroreceptor gain occurs independent of the minimal or lack of recovery of baroreflex control over HR.     

Cyclooxygenase inhibition and baroreflex sensitivity in humans

Animal studies suggest that prostanoids (i.e., such as prostacyclin) may sensitize or impair baroreceptor and/or baroreflex responsiveness depending on the site of administration and/or inhibition. We tested the hypothesis that acute inhibition of cyclooxygenase (COX), the rate-limiting enzyme in prostanoid synthesis, impairs baroreflex regulation of cardiac period (R-R interval) and muscle sympathetic nerve activity (MSNA) in humans and augments pressor reactivity. Baroreflex sensitivity (BRS) was determined at baseline (preinfusion) and 60 min after (postinfusion) intravenous infusion of a COX antagonist (ketorolac; 45 mg) (24 +/- 1 yr; n = 12) or saline (25 +/- 1 yr; n = 12). BRS was assessed by using the modified Oxford technique (bolus intravenous infusion of nitroprusside followed by phenylephrine). BRS was quantified as the slope of the linear portion of the 1) R-R interval-systolic blood pressure relation (cardiovagal BRS) and 2) MSNA-diastolic blood pressure relation (sympathetic BRS) during pharmacological changes in arterial blood pressure. Ketorolac did not alter cardiovagal (19.4 +/- 2.1 vs. 18.4 +/- 2.4 ms/mmHg preinfusion and postinfusion, respectively) or sympathetic BRS (-2.9 +/- 0.7 vs. -2.6 +/- 0.4 arbitrary units.beat(-1).mmHg(-1)) but significantly decreased a plasma biomarker of prostanoid generation (plasma thromboxane B2) by 53 +/- 11%. Cardiovagal BRS (21.3 +/- 3.8 vs. 21.2 +/- 3.0 ms/mmHg), sympathetic BRS (-3.4 +/- 0.3 vs. -3.2 +/- 0.2 arbitrary units.beat(-1).mmHg(-1)), and thromboxane B2 (change in -1 +/- 12%) were unchanged in the control (saline infusion) group. Pressor responses to steady-state incremental (0.5, 1.0, and 1.5 microg.kg(-1).min(-1)) infusion (5 min/dose) of phenylephrine were not altered by ketorolac (n = 8). Collectively, these data indicate that acute pharmacological antagonism of the COX enzyme does not impair BRS (cardiovagal or sympathetic) or augment pressor reactivity in healthy young adults.     

Analysis of afferent,central, and efferent components of the baroreceptor reflex in mice

Studies of genetically modified mice provide a powerful approach to investigate consequences of altered gene expression in physiological and pathological states. The goal of the present study was to characterize afferent, central, and efferent components of the baroreceptor reflex in anesthetized Webster 4 mice. Baroreflex and baroreceptor afferent functions were characterized by measuring changes in renal sympathetic nerve activity (RSNA) and aortic depressor nerve activity (ADNA) in response to nitroprusside- and phenylephrine-induced changes in arterial pressure. The data were fit to a sigmoidal logistic function curve. Baroreflex diastolic pressure threshold (P(th)), the pressure at 50% inhibition of RSNA (P(mid)), and baroreflex gain (maximum slope) averaged 74 +/- 5 mmHg, 101 +/- 3 mmHg, and 2.30 +/- 0.54%/mmHg, respectively (n = 6). The P(th), P(mid), and gain for the diastolic pressure-ADNA relation (baroreceptor afferents) were similar to that observed for the overall reflex averaging 79 +/- 9 mmHg, 101 +/- 4 mmHg, and 2.92 +/- 0.53%/mmHg, respectively (n = 5). The central nervous system mediation of the baroreflex and the chronotropic responsiveness of the heart to vagal efferent activity were independently assessed by recording responses to electrical stimulation of the left ADN and the peripheral end of the right vagus nerve, respectively. Both ADN and vagal efferent stimulation induced frequency-dependent decreases in heart rate and arterial pressure. The heart rate response to ADN stimulation was nearly abolished in mice anesthetized with pentobarbital sodium (n = 4) compared with mice anesthetized with ketamine-acepromazine (n = 4), whereas the response to vagal efferent stimulation was equivalent under both types of anesthesia. Application of these techniques to studies of genetically manipulated mice can be used to identify molecular mechanisms of baroreflex function and to localize altered function to afferent, central, or efferent sites.     

Increased blood pressure in the offspring of diabetic mothers

Studies were conducted in rats to determine the effect of maternal diabetes and the consequent hyperglycemia on cardiovascular function in the offspring. Diabetes was induced in pregnant Wistar rats through streptozotocin injection (50 mg/kg). Cardiovascular parameters were measured in 2-mo-old offspring animals of diabetic (OD, n=12) and control rats (OC, n=8). Arterial pressure (AP), heart rate (HR), baroreflex sensitivity, and vascular responsiveness to phenylephrine (PH) and sodium nitroprusside (SN) were measured. Angiotensin-converting enzyme (ACE) activity in heart, kidney, and lung was determined. OD rats exhibited increases in systolic AP (138+/-8 vs. 119+/-6 mmHg, OD vs. OC), with no change in HR (342+/-21 vs. 364+/-39 beats per minute (bpm), OD vs. OC). The reflex tachycardia elicited by SN was reduced in OD rats, as indicated by the slope of the linear regression (-2.2+/-0.4 vs. -3.6+/-0.8 bpm/mmHg, OD vs. OC). Vascular responsiveness to PH was increased 63% in OD rats compared with OC. OD rats showed increases in ACE activity in heart, kidney, and lung (1.13+/-0.24, 3.04+/-0.86, 40.8+/-8.9 vs. 0.73+/-0.19, 1.7+/-0.45, 28.1+/-6 nmol His-Leu.min-1 mg protein-1, OD vs. OC). Results suggest that diabetes during pregnancy affects cardiovascular function in offspring, seen as hypertension, baroreflex dysfunction, and activation of tissue renin-angiotensin system.     

Glucocorticoids modulate baroreflex control of renal sympathetic nerve activity

Experiments were performed to determine the effects of glucocorticoids on arterial baroreceptor reflex control of renal sympathetic nerve activity (RSNA). Intravenous infusions of phenylephrine and nitroprusside were used to produce graded changes in arterial pressure (AP) in Inactin-anesthetized male Sprague-Dawley rats. Baroreflex control of RSNA was determined during a baseline period and 2 and 3 h after administration of the glucocorticoid type II receptor antagonist Mifepristone (30 mg/kg sc) or vehicle (oil). Corticosterone (cort) treatment (100 mg cort pellet sc for 2-3 wk) increased baseline AP from 115 +/- 2 to 128 +/- 1 mmHg. Cort treatment also decreased the gain coefficient and increased the midpoint of the baroreflex curve. Treatment of cort rats with Mifepristone decreased AP within 2 h and increased the gain coefficient and decreased the midpoint of the baroreflex function curve back toward values measured in control rats. Mifepristone altered the baroreflex function curve even when AP was maintained at baseline levels. Therefore, these data demonstrate for the first time that glucocorticoids can modulate baroreflex control of RSNA by a mechanism that is, in part, independent of changes in AP.     

Central cardiovascular effects of baclofen in spontaneously hypertensive rats

This study was conducted to investigate the effects of centrally administered baclofen on blood pressure and heart rate in conscious spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Administration of baclofen (1.0 microgram/kg) into the lateral cerebral ventricle (icv) produced an increase in mean arterial pressure (MAP) in both SHR and WKY rats. The increase in MAP was significantly lower in SHR (13 +/- 3 mmHg) when compared with WKY (27 +/- 5 mmHg). The changes in heart rate (HR) were variable, from no change to a very small increase and did not differ significantly between SHR and WKY rats. The ability of baclofen to interfere with baroreceptor reflexes was also tested in separate experiments. In SHR, icv injection of baclofen (1.0 microgram/kg) significantly suppressed the pressor response and bradycardia evoked by phenylephrine 3.0 micrograms/kg iv, whereas in WKY, the pressor and HR responses to similar injections of phenylephrine were not affected by icv baclofen. Similarly, baclofen treatment modified hypotensive response and reflex tachycardia induced by nitroprusside (10.0 micrograms/kg) iv in SHR but not in WKY rats. Administration of sympathetic ganglionic blocker hexamethonium (HEX; 25 mg/kg) iv produced an equivalent decrease in MAP between SHR and WKY following icv injection of baclofen (1.0 microgram/kg). These results suggest that the effects of baclofen on the baroreceptor reflexes in SHR may not be mediated by a change in peripheral sympathetic tone.     

Control of blood pressure mediated by baroreflex changes of heart rate in the chicken embryo (Gallus gallus)

Pharmacological manipulation of peripheral resistance via sodium nitroprusside and phenylephrine was used to study baroreflex function over the latter two-thirds of incubation in embryonic chickens. From day 9 to day 19 of incubation, there is a positive linear relation between heart rate and blood pressure, indicating the feedforward action of arterial pressure on heart rate. A reciprocal relationship between blood pressure and heart rate became pronounced during the last 3 days of incubation. For the purpose of the study, gain of the baroreflex was calculated as maximal gain (only those embryos that demonstrated the response) or average gain (all embryos). Maximal gain increased progressively from 13 +/- 7 beats. min(-1). kPa(-1) at 18 days to 105 +/- 83 beats. min(-1). kPa(-1) in 2-day-old hatchlings. The percentage of embryos older than 18 days with baroreflex responses increased from 33% on day 19 to 56% on day 21, indicating that baroreflex regulation begins late in incubation ( approximately 90% incubation time), and the gain of this reflex exhibits a maturation over the final 3 days of incubation.     

Baroreflex control of the rat tail circulation in normothermia and hyperthermia

The role of thermoregulatory background in the baroreceptor reflex control of the tail circulation was investigated 1) in anesthetized rats with a constant flow technique and 2) in conscious rats by measuring tail blood flow (venous occlusion plethysmography). In series I, during normothermia, systemic intravenous phenylephrine infusion increased mean arterial pressure (MAP) by 61.0 +/- 3.6 mmHg and induced a reflex decrease in tail perfusion pressure (TPP) from 105.0 +/- 6.3 to 84.2 +/- 4.4 mmHg (P less than 0.005). Hyperthermia decreased TPP to 66.5 +/- 5.1 mmHg (P less than 0.001) and abolished the TPP response to increased MAP (P greater than 0.05). Increases in MAP via systemic infusion of whole blood caused reductions in TPP during normothermia but failed to reduce TPP further during hyperthermia. Graded decreases in MAP during both normothermia and hyperthermia caused tail vasoconstriction. The increase in TPP was greater (P less than 0.025) during hyperthermia. In series II, conscious animals showed similar responses to hemorrhage. Graded decreases in MAP produced graded decreases in tail vascular conductance (TVC, ml.100 ml-1.min-1.100 mmHg-1). The slope of the TVC-MAP relationship averaged 0.011 +/- 0.003 TVC U/mmHg during normothermia and was markedly steeper (P less than 0.01) during hyperthermia (1.99 +/- 0.39 TVC U/mmHg). Thus the participation of the cutaneous vasculature of the rat in baroreceptor reflexes depends on thermal status, probably through the level of background sympathetic vasoconstrictor nerve activity.     

Cyclosporine attenuates the autonomic modulation of reflex chronotropic responses in conscious rats

Cyclosporine A (CyA), an immunosuppressant drug, has been shown to attenuate the baroreflex control of heart rate (HR). This study investigated whether or not the CyA-induced baroreflex dysfunction is due to alterations in the autonomic (sympathetic and parasympathetic) control of the heart. We evaluated the effect of muscarinic or beta-adrenergic blockade by atropine and propranolol, respectively, on reflex HR responses in conscious rats treated with CyA (20 mg x kg(-1) x day(-1) dissolved in sesame oil) for 11-13 days or the vehicle. Baroreflex curves relating changes in HR to increases or decreases in blood pressure (BP) evoked by phenylephrine (PE) and sodium nitroprusside (NP), respectively, were constructed and the slopes of the curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(NP)). Intravenous administration of PE and NP produced dose-related increases and decreases in BP, respectively, that were associated with reciprocal changes in HR. CyA caused significant (P < 0.05) reductions in reflex HR responses as indicated by the smaller BRS(PE) (-0.97 +/- 0.07 versus -1.47 +/- 0.10 beats x min(-1) x mmHg(-1) (1 mmHg = 133.322 Pa)) and BRS(NP) (-2.49 +/- 0.29 versus -5.23 +/- 0.42 beats x min(-1) x mmHg(-1)) in CyA-treated versus control rats. Vagal withdrawal evoked by muscarinic blockade elicited significantly lesser attenuation of BRS(PE) in CyA compared with control rats (40.2 +/- 8.0 versus 57.7 +/- 4.4%) and abolished the BRS(PE) difference between the two groups, suggesting that CyA reduces vagal activity. CyA also appears to impair cardiac sympathetic control because blockade of beta-adrenergic receptors by propranolol was less effective in reducing reflex tachycardic responses in CyA compared with control rats (41.6 +/- 4.2 versus 59.5 +/- 4.5%). These findings confirm earlier reports that CyA attenuates the baroreceptor control of HR. More importantly, the study provides the first pharmacological evidence that CyA attenuates reflex chronotropic responses via impairment of the autonomic modulation of the baroreceptor neural pathways.     

Comparison of two methods of altering blood pressures for assessing neonatal cerebral blood flow autoregulation

The cerebral blood flow of newborn lambs at reduced and elevated arterial blood pressures, induced by intravenous infusion of sodium nitroprusside and phenylephrine hydrochloride as well as blood withdrawal and reinfusion, were compared. Both blood withdrawal and sodium nitroprusside infusion reduced mean arterial pressure from 83 to 60 mmHg (1 mmHg = 133 Pa). Reinfusion of blood increased arterial pressure to 94 mmHg. Phenylephrine hydrochloride infusion increased arterial pressure to 102 mmHg. The cerebral blood flows at corresponding arterial pressures were similar (coefficient of correlation = 0.88, P less than 0.01). Cerebral blood flow before and after infusion of phenylephrine hydrochloride and sodium nitroprusside into the brain via the carotid artery did not change. The results indicate that blood-borne phenylephrine hydrochloride and sodium nitroprusside, in concentrations that would alter arterial blood pressure significantly from its resting level, do not change cerebral blood flow directly.     

兔肾性高血压时的动脉压力感受器反射

14只雄性家兔在双肾缩扎术后12周,经氨基甲酸乙酯静脉麻醉,分别在缓冲神经完整、切断两侧减压神经或切断两侧窦神经后静注新福林或硝普钠升降血压以改变动脉压力感受器活动,观察其心率、后肢血管阻力和肾交感神经活动的反射性变化,并与正常血压兔的反射效应相比较。主要结果如下:(1) 动物双肾动脉缩扎后12周,平均动脉血压(131±9mmHg)较正常动物血压(95±10mmHg)有显著升高(P<0.001);(2) 缓冲神经完整时,新福林和硝普钠升降血压诱发的心率反射性变化与正常血压动物相比显著减弱(P<0.001),而后肢血管阻力和肾交感神经活动的反射性调节无明显改变,表明肾性高血压动物的心率反射性调节与外周循环的反射性调节机能不相平行;而由股动脉内直接注射新福林或硝普钠时,股动脉灌流压的增减幅度与正常血压动物相比并无明显差异;(3) 切断两侧减压神经或切断两侧窦神经后,在正常动物仅使反射性心率调节作用减弱,而后肢血管阻力和肾交感神经活动的反射性调节无明显改变;但在高血压动物,除心率的反射性调节进一步减弱外,新福林和硝普钠升降血压时后肢血管阻力和肾交感神经活动的反射性调节效应也显著地减弱(P<0.001),提示肾性高血压时动脉压力感受器反射的潜在调节能力降低。由此似表明,肾性高血压时动脉压力感受器反射     

Exercise training changes autonomic cardiovascular balance in mice.

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of heart rate were measured in conscious, unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk). Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine, respectively. Autonomic control of heart rate and intrinsic heart rate were determined by use of methylatropine and propranolol. Resting bradycardia was observed in trained mice compared with sedentary animals [485 +/- 9 vs. 612 +/- 5 beats/min (bpm)], whereas mean arterial pressure was not different between the groups (106 +/- 2 vs. 108 +/- 3 mmHg). Baroreflex-mediated tachycardia was significantly enhanced in the trained group (6.97 +/- 0.97 vs. 1.6 +/- 0.21 bpm/mmHg, trained vs. sedentary), whereas baroreflex-mediated bradycardia was not altered by training. The tachycardia induced by methylatropine was significantly increased in trained animals (139 +/- 12 vs. 40 +/- 9 bpm, trained vs. sedentary), whereas the propranolol effect was significantly reduced in the trained group (49 +/- 11 vs. 97 +/- 11 bpm, trained vs. sedentary). Intrinsic heart rate was similar between groups. In conclusion, dynamic exercise training in mice induced a resting bradycardia and an improvement in baroreflex-mediated tachycardia. These changes are likely related to an increased vagal and decreased sympathetic tone, similar to the exercise response observed in humans.     

Atrial natriuretic peptide inhibits compensatory responses when cardiac performance is depressed.

We tested the hypothesis that the atrial natriuretic peptide (ANP) mediated decrease in baroreceptor sensitivity that is seen in normal rats is more pronounced in a state of depressed cardiac performance. Holtzman rats (n = 15) were injected with Adriamycin (1 mg/kg i.p. 3 times/week for 8-10 weeks). Control rats (n = 17) were injected with 0.9% saline. Experiments were done in conscious animals that had been catheterized for i.v. infusions and for measurement of arterial blood pressure (ABP) and heart rate (HR). ANP (250 ng.kg-1.min-1) or saline vehicle was infused i.v. Graded periodic bolus injections of phenylephrine or sodium nitroprusside were given to assess baroreceptor sensitivity (beats.min-1.mmHg-1) up to 60 mmHg (1 mmHg = 133.3 Pa) above and below resting ABP. The following day the experiment was repeated with the ANP-vehicle regimen reversed. Finally, the rats were anesthetized and the rate of left ventricular pressure increase (dP/dt) was measured. Data evaluation included calculation of least squares linear regression slopes of peak delta HR vs. peak delta ABP, applying corrections for experimental errors in both the dependent and independent variables. Adriamycin rats (A) did not differ significantly from control rats (C) with respect to either initial ABP (A = 105 +/- 5; C = 100 +/- 3; mean mmHg +/- SEM) or initial HR (335 +/- 9 vs. 312 +/- 13 beats.min-1). However, their indices of cardiac performance were significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary vasodilation with structurally altered pulmonary vessels and pulmonary hypertension

To evaluate pulmonary vasodilation in a structurally altered pulmonary vascular bed, we gave endothelium-dependent (acetylcholine) and endothelium-independent [sodium nitroprusside, prostaglandin I2 (PGI2)] vasodilators in vivo and to isolated lobar pulmonary arteries from neonatal calves with severe pulmonary hypertension. Acetylcholine, administered by pulmonary artery infusion, decreased pulmonary arterial pressure from 120 +/- 7 to 71 +/- 6 mmHg and total pulmonary resistance from 29.4 +/- 2.6 to 10.4 +/- 0.9 mmHg.l-1.min without changing systemic arterial pressure (90 +/- 5 mmHg). Although both sodium nitroprusside and PGI2 lowered pulmonary arterial pressure to 86 +/- 4 and 96 +/- 4 mmHg, respectively, they also decreased systemic arterial pressure to 65 +/- 4 and 74 +/- 3 mmHg, respectively. Neither sodium nitroprusside nor PGI2 was as effective as acetylcholine at lowering total pulmonary resistance (18.0 +/- 3.6 and 19.1 +/- 2.2 mmHg.l-1.min, respectively). Right-to-left cardiac shunt through the foramen ovale was decreased by acetylcholine from 1.6 +/- 0.4 to 0.1 +/- 0.2 l/min but was not changed by sodium nitroprusside or PGI2. Isolated lobar pulmonary arteries from pulmonary hypertensive calves did not relax in response to acetylcholine, whereas isolated pulmonary arteries from age-matched control calves did relax in response to acetylcholine. Control and pulmonary hypertensive lobar pulmonary arteries relaxed equally well in response to sodium nitroprusside. We concluded that acetylcholine vasodilation was impaired in vitro in isolated lobar pulmonary arteries but was enhanced in vivo in resistance pulmonary arteries in neonatal calves with pulmonary hypertension.     

Physically active lifestyle enhances vagal-cardiac function but not central autonomic neural interaction in elderly humans

The cause of the age-related impairment of arterial baroreflex function remains ill-defined; moreover, it is unknown whether this impairment results from aging per se or from an inactive lifestyle associated with aging. In this study, we sought to: 1) determine whether elderly individuals who maintained an active lifestyle had an enhanced carotid baroreflex function as compared with their sedentary counterparts; and 2) determine whether this difference was due in part to altered function of the arterial baroreceptor and/or altered central modulation. Eight healthy, sedentary (SED, 68+/-2 yr) and eight physically active (ACT, 68+/-1 yr) elderly men with peak O(2) consumption 25.5+/-1.2 vs 35.7+/-2.4 ml/min/kg (P<0.01), respectively, were assessed with carotid baroreceptor (CBR) function using 5s pulses of neck pressure or suction (ranging from +40 to -80 Torr) delivered to the carotid sinus region at rest and during lower body negative pressure (LBNP) of -15 and -40 Torr. Changes in heart rate (HR) and mean arterial pressure (MAP) were assessed for CBR-HR and CBR-MAP gains, respectively. Overall CBR-HR gains in a range of approximately 120 mmHg of carotid sinus pressure were greater (P<0.01) in ACT than SED at rest and during LBNP. The derived peak CBR-HR slopes between ACT and SED at rest were -0.32+/-0.07 vs -0.11+/-0.02 bpm/mmHg (P=0.007), respectively. However, there was no statistical difference (P=0.37) in CBR-MAP gains between the groups. Neither CBR-MAP (P=0.08) nor CBR-HR (P=0.41) gain was augmented by LBNP in the elderly. CONCLUSION: Active lifestyle enhances the CBR-HR reflex sensitivity as a result of the improved vagal-cardiac function in elderly people. Aging is associated with an absence of central autonomic interaction in the control of blood pressure regardless of physical fitness.     

Changes in baroreflex control of renal sympathetic nerve activity in high-fat-fed rats as a predictor of hypertension

There is evidence that obesity is associated with increased sympathetic activity and hypertension. However, the mechanisms responsible for these changes are not fully understood. Therefore, the aim of the present study was to evaluate the cardiovascular function and the baroreceptor reflex control of renal sympathetic nerve activity (rSNA) in rats exposed to a high-fat diet over different periods (10 and 20 weeks) compared to control rats. Serum leptin levels were assessed for all time points. Male Wistar rats weighing 150-180 g were used. Four groups of rats were studied: control 10 weeks (Ct10), obese 10 weeks (Ob10), control 20 weeks (Ct20), and obese 20 weeks (Ob20). Blood pressure (BP) and rSNA were recorded in urethane-anesthetized rats (1.4 g/kg, intravenous).The sensitivity of rSNA responses to baroreceptor reflex was assessed by changes in BP induced by increasing doses of phenylephrine or sodium nitroprusside. Significant and progressive increases in serum leptin levels were found in the obese rats, but not in the control rats. No changes in basal BP or rSNA were found in the Ob10 and Ob20 groups; however, a significant impairment in the baroreceptor sensitivity was observed in the Ob20 group for phenylephrine (slope Ob20: -0.78 ± 0.12 vs. Ct20: -1.00 ± 0.08 potential per second (pps)/mm Hg, P < 0.05) and sodium nitroprusside (slope Ob20: -0.82 ± 0.09 vs. 1.13 ± 0.13 pps/mm Hg, P < 0.05). The results suggest that the baroreceptor dysfunction that controls the rSNA is an initial change in the obesity induced in high-fat-fed rats, which might be a predictor of sympathoexcitation and hypertension associated to obesity.     

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.