Effect of neuromuscular blocking drugs on arterial pressure and heart rate in rats

The effects of neuromuscular blocking drugs on mean arterial pressure (MAP) and heart rate (HR) were studied in rats which were anaesthetised, tracheotomized and ventilated artificially. The arterial pressure was recorded from the carotid artery. Seven neuromuscular blocking drugs were injected intravenously at doses of 1, 5, and 25 mumol/kg. d-Tubocurarine, alcuronium and vecuronium lowered MAP in a dose dependent manner (maximum 40%). Succinylcholine, 1 mumol/kg, reduced MAP and HR, whereas the two larger doses increased them. Gallamine, 25 mumol/kg, or metocurine and pancuronium, 1 or 5 mumol/kg, each, induced short-lasting rises in MAP. Pancuronium, 25 mumol/kg, decreased MAP by 25%, while the largest dose of metocurine appeared to be toxic. The cardiovascular responses to neuromuscular blocking drugs were antagonized or abolished by pretreatment with the ganglionic blocking agent pentolinium. Pentolinium itself markedly reduced MAP and HR. After ganglionic blockade and restoration of MAP by noradrenaline infusion, all the neuromuscular blocking drugs induced short-lasting increases in MAP (10-30%), except d-tubocurarine which still reduced MAP by 30%, a fall which, in contrast to the effect in the absence of the pretreatments, was transient. This response to d-tubocurarine could not be abolished by a combined pretreatment with H1 and H2 antagonists showing that the hypotensive effect of this drug was not due to the liberation of histamine. These results suggest that the cardiovascular responses to neuromuscular blocking drugs in rats might be partly due to ganglionic effects. Other mechanisms are also involved since after the restoration of blood pressure by noradrenaline during the ganglionic blockade some cardiovascular responses to these drugs still occurred.     

最后区注射腺苷对大鼠血压,心率和肾交感神经放电影响

The effects of microinjection of adenosine (Ado) into area postrema (AP) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were examined in 53 anesthetized Sprague Dawley rats. The results obtained are as follows. (1) Following microinjection of Ado (1 ng/60 nl) into AP, MAP, HR and RSNA were decreased from 13.76+/-0.46 kPa, 356.28+/-4.25 bpm and 100+/-0% to 11.23+/-0.49 kPa (P<0.001), 336.91+/-5.23 bpm (P<0.01) and 70.95+/-5.19% (P<0.001), respectively; (2) 8-phenyltheophylline (150 microgram/kg, 0.2 ml,iv), a nonselective adenosine receptor antagonist, and 8-cyclopentyl-1,3-dipropylxanthine (500 microgram/kg, 0.2 ml, iv), a selective A(1) adenosine receptor antagonist, blocked the inhibitory effect of Ado completely; and (3) glibenclamide (5 mg/kg, 0.2 ml, iv), a blocker of ATP-sensitive potassium channel, also abolished the effect of Ado. The above results indicate that microinjection of Ado into AP induces inhibitory effects on MAP, HR and RSNA, which may be related to activation of ATP-sensitive potassium channels mediated by A(1) receptors.     

最后区注射腺苷对大鼠血压、心率和肾交感神经放电的影响

在 5 3只麻醉Sprague Dawley大鼠观察了最后区内微量注射腺苷 (1ng/ 6 0nl)对平均动脉压 (MAP)、心率(HR)和肾交感神经放电 (RSNA)的影响。实验结果如下 :(1)最后区内微量注射Ado后 ,MAP、HR和RSNA分别由13 76± 0 46kPa、35 6 2 8± 4 2 5bpm和 10 0± 0 %下降至 11 2 3± 0 49kPa (P <0 0 0 1)、336 91± 5 2 3bpm (P <0 0 1)和70 95± 5 19% (P <0 0 0 1) ;(2 )静脉注射非选择性腺苷受体拮抗剂 8 苯茶碱 (8 phenyltheophylline,15 0 μg/kg ,0 2ml)和选择性腺苷A1受体拮抗剂 (8 cyclopentyl 1,3 dipropylxanthine,5 0 0 μg /kg ,0 2ml)后 ,腺苷的上述抑制效应可被完全阻断 ;(3)静脉注射ATP敏感性钾通道阻断剂格列苯脲 (5mg/kg ,0 2ml)后 ,腺苷的上述效应也被消除。以上结果提示 ,最后区微量注射腺苷对血压、心率和肾交感神经放电有抑制作用 ,此作用与A1受体介导的ATP敏感性钾通道开放有关。     

Dynamics of sympathetic baroreflex control of arterial pressure in rats

By a white noise approach, we characterized the dynamics of the sympathetic baroreflex system in 11 halothane-anesthetized rats. We measured sympathetic nerve activity (SNA) and systemic arterial pressure (SAP), while carotid sinus baroreceptor pressure (BRP) was altered randomly. We estimated the transfer functions from BRP to SNA (mechanoneural arc), from SNA to SAP (neuromechanical arc), and from BRP to SAP (total arc). The gain of the mechanoneural arc gradually increased about threefold as the frequency of BRP change increased from 0.01 to 0.8 Hz. In contrast, the gain of the neuromechanical arc rapidly decreased to 0.4% of the steady-state gain as the frequency increased from 0.01 to 1 Hz. Although the total arc also had low-pass characteristics, the rate of attenuation in its gain was significantly slower than that of the neuromechanical arc, reflecting the compensatory effect of the mechanoneural arc for the sluggish response of the neuromechanical arc. We conclude that the quantitative estimation of the baroreflex dynamics is vital for an integrative understanding of baroreflex function in rats.     

Baroreceptor reflex control of heart rate in rats studied by induced and autogenic changes in arterial pressure

The function of the arterial baroreflex has traditionally been assessed by measurement of reflex changes in heart rate (HR) or sympathetic nerve activity resulting from experimenter-induced manipulation of arterial blood pressure (the Oxford method, also termed the pharmacological method). However, logistical and flexibility limitations of this technique have promoted the development of new methods for assessing baroreflex function such as the evaluation of changes in spontaneous arterial pressure and HR. Although this new spontaneous method has been validated in dogs and humans, it has not been rigorously tested in rats. In the present study, the method of correlating spontaneous changes in systolic blood pressure and HR was evaluated in resting, normotensive Sprague-Dawley rats. This technique was found to be neither reliable nor valid under the conditions employed in the present protocol. We also tested a variation of the spontaneous method that evaluates particular sequences of data during which arterial pressure and pulse interval are changing in the same direction for at least three consecutive heartbeats (the sequence method). The sequence method did not provide extra reliability or validity over the spontaneous method. We conclude that due to the restricted range of variability obtained by measuring spontaneous blood pressure fluctuations, the spontaneous and sequence techniques do not provide data that are comparable to the traditional method of assessing HR changes triggered by arterial blood pressure increases and decreases induced by vasoactive drugs. However, it is possible that surgical stress obscured the relationship between blood pressure and HR, and therefore additional studies are needed to determine whether the spontaneous and sequence methods can be applied to rats during different behavioral states.     

Effects of nNOS antisense in the paraventricular nucleus on blood pressure and heart rate in rats with heart failure

Using neuronal NO synthase (nNOS)-specific antisense oligonucleotides, we examined the role of nitric oxide (NO) in the paraventricular nucleus (PVN) on control of blood pressure and heart rate (HR) in conscious sham rats and rats with chronic heart failure (CHF). After 6-8 wk, rats with chronic coronary ligation showed hemodynamic and echocardiographic signs of CHF. In sham rats, we found that microinjection of sodium nitroprusside (SNP, 20 nmol, 100 nl) into the PVN induced a significant decrease in mean arterial pressure (MAP). SNP also induced a significant decrease in HR over the next 10 min. In contrast, the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 200 pmol, 100 nl) significantly increased MAP and HR over the next 18-20 min. After injection of nNOS antisense, MAP was significantly increased in sham rats over the next 7 h. The peak response was 27.6 +/- 4.1% above baseline pressure. However, in the CHF rats, only MAP was significantly increased. The peak magnitude was 12.9 +/- 5.4% of baseline, which was significantly attenuated compared with sham rats (P < 0.01). In sham rats, the pressor response was completely abolished by alpha-receptor blockade. HR was significantly increased from hour 1 to hour 7 in sham and CHF rats. There was no difference in magnitude of HR responses. The tachycardia could not be abolished by the beta(1)-blocker metoprolol. However, the muscarinic receptor antagonist atropine did not further augment the tachycardia. We conclude that NO induces a significant depressor and bradycardiac response in normal rats. The pressor response is mediated by an elevated sympathetic tone, whereas the tachycardia is mediated by withdrawal of parasympathetic tone in sham rats. These data are consistent with a downregulation of nNOS within the PVN in CHF.     

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the alpha index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2 to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1 ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.     

Histamine receptor H1 in the nucleus tractus solitarii regulates arterial pressure and heart rate in rats

Axons of histamine (HA)-containing neurons are known to project from the posterior hypothalamus to many areas of the brain, including the nucleus tractus solitarii (NTS), a central brain structure that plays an important role in regulating arterial pressure. However, the functional significance of NTS HA is still not fully established. In this study, we microinjected HA or 2-pyridylethylamine, a HA-receptor H(1)-specific agonist, into the NTS of urethane-anesthetized Wister rats to identify the potential functions of NTS HA on cardiovascular regulation. When HA or H(1)-receptor-specific agonist was bilaterally microinjected into the NTS, mean arterial pressure (MAP) and heart rate (HR) were significantly increased, whereas pretreatment with the H(1)-receptor-specific antagonist cetirizine into the NTS significantly inhibited the cardiovascular responses. The maximal responses of MAP and HR changes induced by HA or H(1)-receptor-specific agonist were dose dependent. We also confirmed gene expression of HA receptors in the NTS and that the expression level of H(1) mRNA was higher than that of the other subtypes. In addition, we found that H(1) receptors are mainly expressed in neurons of the NTS. These findings suggested that HA within the NTS may play a role in regulating cardiovascular homeostasis via activation of H(1) receptors expressed in the NTS neurons.     

Effects of microgravity elicited by parabolic flight on abdominal aortic pressure and heart rate in rats.

Abdominal aortic pressure (AAP), heart rate (HR), and aortic nerve activity (ANA) during parabolic flight were measured by using a telemetry system to clarify the acute effect of microgravity (microG) on hemodynamics in rats. While the animals were conscious, AAP increased up to 119 +/- 3 mmHg on exposure to microG compared with the value at 1 G (95 +/- 3 mmHg; P < 0.001), whereas AAP decreased immediately on exposure to microG under urethane anesthesia (microG: 72 +/- 9 mmHg vs. 1 G: 78 +/- 8 mmHg; P < 0.05). HR also increased during microG in conscious animals (microG: 349 +/- 12 beats/min vs. 1 G: 324+9 beats/min; P < 0.01), although no change was observed under anesthesia. ANA, which was measured under anesthesia, decreased in response to acute microG exposure (microG: 33 +/- 7 counts/s vs. 1 G: 49 +/- 5 counts/s; P < 0.01). These results suggest that microG essentially induces a decrease of arterial pressure; however, emotional stress and body movements affect the responses of arterial pressure and HR during exposure to acute microG.     

延髓腹外侧头端区注射肾上腺髓质素对大鼠血压、心率和肾交感神经活动的影响

本研究在 3 4只麻醉Sprague Dawley大鼠观察了延髓腹外侧头端区内微量注射肾上腺髓质素 ( 10μmol/L ,2 0 0nl)对平均动脉压 (MAP)、心率 (HR)和肾交感神经放电 (RSNA)的影响。实验结果如下 :( 1)延髓腹外侧头端区内微量注射肾上腺髓质素可引起MAP、HR、和RSNA明显增加 ,分别由 99 0 9± 3 3 2mmHg ,3 70 78± 7 84bpm和 10 0± 0 %增至 113 5 7± 3 64mmHg (P <0 0 0 1) ,3 83 2 8± 7 3 8bpm (P <0 0 0 1)和 12 3 72±2 74% (P <0 0 0 1) ;( 2 )降钙素基因相关肽受体阻断剂CGRP8 3 7( 10 0 μmol/L ,2 0 0nl)不能阻断肾上腺髓质素的上述效应 ;( 3 )静脉注射NO前体L 精氨酸 ( 10 0mg/kg ,0 2ml)可消除肾上腺髓质素的上述效应。以上结果提示 ,肾上腺髓质素作用于延髓腹外侧头端区可产生显著的心血管作用 ,此作用不是由降钙素基因相关肽受体介导 ,但可被NO所阻断     

Relationship between renal sympathetic nerve activity and arterial pressure during REM sleep in rats

The relationship between renal sympathetic nerve activity (RSNA) and systemic arterial pressure obtained during rapid eye movement (REM) sleep was compared with that obtained in other sleep and awake states. Electrodes for the measurements of RSNA, electrocardiogram, electromyogram, and electroencephalogram and a catheter for the measurement of systemic arterial pressure were implanted while the animals were under aseptic conditions at least 5 days before the experiment. During the transition from non-REM (NREM) to REM sleep, RSNA and heart rate (HR) decreased immediately by 46 +/- 2% (P < 0.05) and 22 +/- 3 beats/min (P < 0.05), respectively, over 3 s after the onset of REM sleep. Meanwhile, systemic arterial pressure increased gradually after the onset of REM sleep, which was apparently independent of the changes in RSNA. During REM sleep, the relationships between RSNA/HR and systemic arterial pressure were dissociated compared with that obtained during the other behavioral states. These data indicate that the interdependency between systemic arterial pressure and RSNA during REM sleep is likely to be modified compared with other behavioral states.     

Digital heart rate monitor derived from the arterial pressure pulse

This monitor displays heart rate without the need for electrical contact with the experimental animal. The device uses a quartz pressure transducer connected to an arterial catheter and has a full scale accuracy of ± 3 beats min⁻¹; its range is 0–400 beats min⁻¹. There is an output voltage proportional to heart rate and internal calibration facilities are provided at 60 and 360 beats min⁻¹.     

Differential sympathetic outflow elicited by active muscle in rats

The present study was undertaken to test the hypothesis that activation of the muscle reflex elicits less sympathetic activation in skeletal muscle than in internal organs. In decerebrate rats, we examined renal and lumbar (mainly innervating hindlimb blood vessels) sympathetic nerve activities (RSNA and LSNA, respectively) during 1 min of 1) repetitive (1- to 4-s stimulation-to-relaxation) contraction of the triceps surae muscle, 2) repetitive tendon stretch, and 3) repetitive contraction with hindlimb circulatory occlusion. During these interventions, RSNA and LSNA responded synchronously as tension developed. The increase was greater in RSNA than in LSNA [+51 +/- 14 vs. +24 +/- 5% (P < 0.05) with contraction, +46 +/- 8 vs. +17 +/- 4% (P < 0.05) with stretch, +76 +/- 20 vs. 39 +/- 7% (P < 0.05) with contraction during occlusion] during all three interventions: repetitive contraction (n = 10, +508 +/- 48 g tension from baseline), tendon stretch (n = 12, +454 +/- 34 g), and contraction during occlusion (n = 9, +473 +/- 33 g). Additionally, hindlimb circulatory occlusion significantly enhanced RSNA and LSNA responses to contraction. These data demonstrate that RSNA responses to muscle contraction and stretch are greater than LSNA responses. We suggest that activation of the muscle afferents induces the differential sympathetic outflow that is directed toward the kidney as opposed to the limbs. This differential outflow contributes to the distribution of cardiac output observed during exercise. We further suggest that as exercise proceeds, muscle metabolites produced in contracting muscle sensitize muscle afferents and enhance sympathetic drive to limbs and renal beds.     

Effect of hypoxia on arterial baroreflex control of heart rate and muscle sympathetic nerve activity in humans.

We tested the hypothesis that acute hypoxia would alter the sensitivity of arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20-33 yr), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity by using the modified Oxford technique during both normoxia and hypoxia (12% O(2)). Compared with normoxia, hypoxia reduced arterial O(2) saturation levels from 96.8 +/- 0.3 to 80.7 +/- 1.4% (P < 0.001), increased heart rate from 59.8 +/- 2.4 to 79.4 +/- 2.9 beats/min (P < 0.001), increased mean arterial pressure from 96.7 +/- 2.5 to 105.0 +/- 3.3 mmHg (P = 0.002), and increased sympathetic activity 126 +/- 58% (P < 0.05). The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by hypoxia (heart rate: -1.02 +/- 0.09 vs. -1.02 +/- 0.11 beats. min(-1). mmHg(-1); nerve activity: -5.6 +/- 0.9 vs. -6.2 +/- 0.9 integrated activity. beat(-1). mmHg(-1); both P > 0.05). Acute exposure to hypoxia reset baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity.     

Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats

Adiponectin is an adipocytokine that modulates energy homeostasis and glucose metabolism. Here, we examined the effects of acute intravenous (iv) and lateral cerebral ventricular (LCV) injections of adiponectin on the renal sympathetic nerve activity (RSNA) and blood pressure (b/p) in urethane-anesthetized rats. Both iv and LCV injections of adiponectin induced dose-dependent suppressions of RSNA and b/p. Moreover, we found that bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) abolished the effects of iv injection of adiponectin on RSNA and b/p. These findings suggest that adiponectin decreases the RSNA and b/p in a dose-dependent manner and that the SCN is implicated in mechanism of adiponectin actions on RSNA and b/p. These findings also suggest that the hypotensive-action activity of adiponectin is realized, at least partially, via changes in activities of autonomic nerves activity.