Effect of baroreceptor denervation on the autonomic control of arterial pressure in conscious mice

This study evaluated the role of arterial baroreceptors in arterial pressure (AP) and pulse interval (PI) regulation in conscious C57BL mice. Male animals, implanted with catheters in a femoral artery and a jugular vein, were submitted to sino-aortic (SAD), aortic (Ao-X) or carotid sinus denervation (Ca-X), 5 days prior to the experiments. After basal recording of AP, the lack of reflex bradycardia elicited by administration of phenylephrine was used to confirm the efficacy of SAD, and cardiac autonomic blockade with methylatropine and propranolol was performed. The AP and PI variability were calculated in the time and frequency domains (spectral analysis/fast Fourier transform) with the spectra quantified in low- (LF; 0.25-1 Hz) and high-frequency bands (HF; 1-5 Hz). Basal AP and AP variability were higher after SAD, Ao-X or Ca-X than in intact mice. Pulse interval was similar among the groups, whereas PI variability was lower after SAD. Atropine elicited a slight tachycardia in control mice but did not change PI after total or partial denervation. The bradycardia caused by propranolol was higher after SAD, Ao-X or Ca-X compared with intact mice. The increase in the variability of AP was accompanied by a marked increase in the LF and HF power of the AP spectra after baroreceptor denervation. The LF and HF power of the PI were reduced by SAD and by Ao-X or Ca-X. Therefore, both sino-aortic and partial baroreceptor denervation in mice elicits hypertension and a remarkable increase in AP variability and cardiac sympathetic tonus. Spectral analysis showed an important contribution of the baroreflex in the power of LF oscillations of the PI spectra. Both sets of baroreceptors seem to be equally important in the autonomic regulation of the cardiovascular system in mice.     

Intrathecal kynurenate reduces arterial pressure, heart rate and baroreceptor-heart rate reflex in conscious rats

In the present study, an excitatory amino acid (EAA) pathway in the spinal cord which maintains sympathetic vasomotor tone in conscious rats has been investigated. To this end, the cardiovascular effects of an intrathecally administered EAA antagonist, kynurenate (KYN), were studied in conscious rats. KYN (0.5 mumol in 10 microliters) caused a dramatic reduction in mean arterial pressure (MAP) and heart rate (HR) that persisted for 2-3 h, and also resulted in extensor paralysis of the hindlimbs. The time courses of fall in MAP and HR and hindlimb paralysis were similar. Baroreceptor-HR reflex activity was also markedly impaired after KYN, suggesting functional diminution of sympathetic outflow at the level of the spinal cord after blockade of EAA receptors by KYN. Xanthurenate, a metabolite of KYN without EAA antagonistic properties, produced negligible effects at the same dose of KYN. While these findings do not identify the putative EAA pathway, they do provide the first demonstration that this system is tonically active in conscious rats.     

Importance of the renin-angiotensin system in the regulation of arterial blood pressure in conscious mice and rats

AIM: The present experiments were designed to determine the mechanism(s) for increased sensitivity to blockade of the renin-angiotensin system in mice in comparison with rats. METHODS: Mice and rats, with indwelling femoral arterial and venous catheters, were chronically administered angiotensin II or pharmacological inhibitors of the renin-angiotensin system as sodium intake was altered. RESULTS: Increasing sodium intake led to suppression of circulating renin, angiotensin II, and aldosterone in rats and mice in the absence of alterations in arterial blood pressure. Additional experiments demonstrated that continuous intravenous infusion of angiotensin II (20 ng kg(-1) min(-1)) significantly increased arterial blood pressure by approximately 35 mmHg in conscious rats at all levels of sodium intake (n = 6). In contrast, arterial pressure was unaffected by angiotensin II infusion in conscious mice under conditions of low sodium intake, although arterial pressure was increased by 16 mmHg when mice were administered a high sodium intake while infused with angiotensin II (n = 6). In comparison, blockade of the endogenous renin-angiotensin system led to significantly greater effects on arterial pressure in mice than rats. Continuous infusion of captopril (30 microg kg(-1) min(-1)) or losartan (100 microg kg(-1) min(-1)) resulted in a 55-90% greater fall in blood pressure in conscious mice in comparison with conscious rats. CONCLUSION: The present studies indicate that arterial pressure in mice is more dependent upon the endogenous renin-angiotensin system than it is in rats, but mice are more resistant to the hypertensive effects of exogenous angiotensin II.     

Roles of the vestibular system in controlling arterial pressure in conscious rats during a short period of microgravity

In order to evaluate the roles of the vestibular system in controlling arterial pressure (AP) during exposure to a short period of microgravity (microG), the AP was measured in conscious free-moving rats having intact vestibular systems and those having vestibular lesions (FM-Intact and FM-VL groups, respectively). During free drop-induced microG, the AP increased in the FM-Intact group; it was 38+/-4 mmHg more than the AP observed during 1G. However, the increase in AP was significantly lower in the FM-VL group (20+/-2 mmHg). Further, to examine the sudden effect of a body floating in the midair in response to the AP during exposure to muG a body stabilizer was placed on the back of rats having intact vestibular systems and those having vestibular lesions (STAB-Intact and STAB-VL groups, respectively). The increase in the AP was significantly depressed in the STAB-Intact group; when compared with that in the FM-Intact group, but the increase was still significant (27+/-2 mmHg). On the other hand, the increase in the AP was completely eliminated in the STAB-VL group (7+/-5 mmHg). These results indicate that the AP increases during exposure to muG in conscious rats, and the vestibular system and body stability are significantly involved in this response.     

Losartan对慢性低氧大鼠肺动脉压力及管壁胶原的影响

目的：探讨氯沙坦（losartan）对慢性低氧大鼠肺动脉压力及管壁胶原的影响。方法：将二级SD大鼠分为：对照组（A）、低氧组（B）、低氧+losartan组（C），低氧时间为4周。采用透射电镜、免疫组化、原位杂交等方法观察losartan对慢性低氧大鼠肺动脉平均压（mPAP）、右心室重量比（RV/LV+S）、肺细小动脉超微结构、肺动脉管壁Ⅰ、Ⅲ胶原和Ⅰ、Ⅲ前胶原基因的影响。结果：①B组mPAP、RV/LV+S显著高于A组（P<0.01），C组mPAP、RV/LV+S显著低于B组（P<0.01）。②电镜检查显示B组肺动脉胶原纤维较A组明显为多，C组较B组明显为少。③免疫组化、原位杂交显示B组肺细小动脉(直径约100-200μm)Ⅰ型胶原及Ⅰ型前胶原mRNA平均吸光度值显著高于A组（均P<0.01），C组肺细小动脉Ⅰ型胶原及Ⅰ型前胶原mRNA平均吸光度值明显低于B组（均P<0.01），Ⅲ型胶原及Ⅲ型前胶原mRNA平均吸光度值各组间无明显差异（均P>0.05）。结论：losartan可预防慢性低氧肺动脉高压的形成和肺动脉管壁胶原的生成、沉积。     

Effects of dietary copper on human autonomic cardiovascular function

Summary Heart rate and blood pressure responses during supine rest, orthostasis, and sustained handgrip exercise at 30% maximal voluntary contraction were determined in eight healthy women aged 18–36 years who consumed diets varying in copper and ascorbic acid content. Copper retention and plasma copper concentration were not affected by diet. Enzymatic, but not immunoreactive, ceruloplasmin was lower (p<0.05) after the low copper and high ascorbic acid diet periods. Diet had no effect on resting supine heart rates, orthostatic responses in heart rate and blood pressure, or standing resting blood pressure. Systolic and diastolic blood pressures were increased significantly (p<0.05) during the handgrip test at the end of the low copper and ascorbic acid supplementation periods. Also, the ratio of enzymatic to immunoreactive ceruloplasmin decreased significantly during these dietary treatments. The mean arterial blood pressure at the end of the handgrip test was negatively (p<0.0004) correlated with the ceruloplasmin ratios. These findings indicate a functional alteration in human blood pressure regulation during mild copper depletion.     

川芎嗪对慢性低氧高二氧化碳大鼠肺动脉压力及管壁胶原的影响

目的:探讨川芎嗪对慢性低O₂高CO₂大鼠肺动脉压力及肺动脉管壁胶原的影响。方法:将SD大鼠30只分为:对照组(A),低O₂高CO₂组(B),低O₂高CO₂＋川芎嗪组(C),低O₂高CO₂时间为4周。结果:⑴B组肺动脉平均压(mPAP)显著高于A组(P＜0.01),C组mPAP显著低于B组(P＜0.01),3组间平均颈动脉压无显著差异(P＞0.05);⑵电镜显示B组肺动脉胶原纤维较A组明显为多,C组较B组明显为少。免疫组化显示B组肺动脉Ⅰ型胶原含量(平均吸光度值LD)较A组明显为高(P＜0.01),C组较B组明显为低(P＜0.01),Ⅲ型胶原LD各组间无明显差异(P＞0.05);⑶B组血浆内皮素浓度高于A组,血清NO₂^-/NO₃^-低于A组,C组血浆内皮素浓度低于B组,NO₂^-/NO₃^-高于B组,P均＜0.01。结论:川芎嗪可预防慢性低 O₂高CO₂性肺动脉高压的形成和肺动脉管壁胶原的沉积。     

Importance of the renin–angiotensin system in the regulation of arterial blood pressure in conscious mice and rats

Aim: The present experiments were designed to determine the mechanism(s) for increased sensitivity to blockade of the renin–angiotensin system in mice in comparison with rats. Methods: Mice and rats, with indwelling femoral arterial and venous catheters, were chronically administered angiotensin II or pharmacological inhibitors of the renin–angiotensin system as sodium intake was altered. Results: Increasing sodium intake led to suppression of circulating renin, angiotensin II, and aldosterone in rats and mice in the absence of alterations in arterial blood pressure. Additional experiments demonstrated that continuous intravenous infusion of angiotensin II (20 ng kg^?1 min^?1) significantly increased arterial blood pressure by approximately 35 mmHg in conscious rats at all levels of sodium intake (n = 6). In contrast, arterial pressure was unaffected by angiotensin II infusion in conscious mice under conditions of low sodium intake, although arterial pressure was increased by 16 mmHg when mice were administered a high sodium intake while infused with angiotensin II (n = 6). In comparison, blockade of the endogenous renin–angiotensin system led to significantly greater effects on arterial pressure in mice than rats. Continuous infusion of captopril (30 μg kg^?1 min^?1) or losartan (100 μg kg^?1 min^?1) resulted in a 55–90% greater fall in blood pressure in conscious mice in comparison with conscious rats. Conclusion: The present studies indicate that arterial pressure in mice is more dependent upon the endogenous renin–angiotensin system than it is in rats, but mice are more resistant to the hypertensive effects of exogenous angiotensin II.     

Chronic activation of endogenous angiotensin-converting enzyme 2 protects diabetic rats from cardiovascular autonomic dysfunction

In this study, we evaluated whether the activation of endogenous angiotensin-converting enzyme 2 (ACE2) would improve the cardiovascular autonomic dysfunction of diabetic rats. Ten days after induction of type 1 diabetes (streptozotocin, 50 mg kg(-1) i.v.), the rats were treated orally with 1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one (XNT), a newly discovered ACE2 activator (1 mg kg(-1) day(-1)), or saline (equivalent volume) for 30 days. Autonomic cardiovascular parameters were evaluated in conscious animals, and an isolated heart preparation was used to analyse cardiac function. Diabetes induced a significant decrease in the baroreflex bradycardia sensitivity, as well as in the chemoreflex chronotropic response and parasympathetic tone. The XNT treatment improved these parameters by ≈ 76% [0.82 ± 0.09 versus 1.44 ± 0.17 Ratio between changes in pulse interval and changes in mean arterial pressure (ΔPI/ΔmmHg)], ～85% (-57 ± 9 versus -105 ± 10 beats min(-1)) and ≈ 205% (22 ± 2 versus 66 ± 12 beats min(-1)), respectively. Also, XNT administration enhanced the bradycardia induced by the chemoreflex activation by v 74% in non-diabetic animals (-98 ± 16 versus -170 ± 9 Δbeats min(-1)). No significant changes were observed in the mean arterial pressure, baroreflex tachycardia sensitivity, chemoreflex pressor response and sympathetic tone among any of the groups. Furthermore, chronic XNT treatment ameliorated the cardiac function of diabetic animals. However, the coronary vasoconstriction observed in diabetic rats was unchanged by ACE2 activation. These findings indicate that XNT protects against the autonomic and cardiac dysfunction induced by diabetes. Thus, our results provide evidence for the viability and effectiveness of oral administration of an ACE2 activator for the treatment of the cardiovascular autonomic dysfunction caused by diabetes.     

Waning cardiovascular responses to adrenergic drugs in conscious ageing rats.

Blood pressure and heart rate responses to various drugs were recorded in three groups of conscious rats at ages 3-, 12- and 26-months to determine whether cardiovascular responsiveness changes selectively with age. Basal mean pressures were higher while heart rates were lower in 26-month-old rats than in others. Phenylephrine, as an alpha-adrenergic agonist, produced significantly smaller pressor and bradycardic responses in 26-month-old than in younger rats. By contrast, pressor and bradycardic responses to angiotensin did not differ between age groups. Depressor responses produced by isoproterenol, as a beta-adrenergic agonist, were unaffected by age, but the accompanying tachycardia was significantly weaker in 26-month-old than in younger rats. On the other hand, combined alpha- and beta-adrenergic stimulation with epinephrine elicited pressor and bradycardic responses that were significantly smaller in 12- and 26-month-old rats than in 3-month-old rats. Thus, our results show that while vascular alpha-adrenergic and myocardial beta-adrenergic responses diminished with age, cardiovascular responses to angiotensin were essentially unaltered. Considered collectively these results suggest that ageing impairs responsiveness to alpha- and beta-adrenergic stimuli selectively without affecting that to other vasoactive drugs probably because as endogenous catecholamines increase with age, receptor occupancy also increases and the respective vascular and myocardial receptors become saturated.     

Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

OBJECTIVES:

The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life.

METHOD:

The animals were assigned to control (control, n = 10) and monosodium glutamate (monosodium glutamate, n = 13) groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol.

RESULTS:

Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%), an increased area under the curve of total insulin secretion during glucose overload (39.3%), and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times), bradycardic responses (>4 times), and vagal (∼38%) and sympathetic effects (∼36%) were reduced as compared to the control group.

CONCLUSION:

Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.     

Spontaneous variations in arterial blood pressure, heart rate and sympathetic nerve activity in conscious normotensive and spontaneously hypertensive rats

In the present study we have recorded spontaneous variations in mean arterial blood pressure (MAP), heart rate (HR) and mean rectified splanchnic nerve activity (SNA) in conscious undisturbed normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The variability in blood pressure was not significantly different but HR variability tended to be lower in SHR. The variability in SNA expressed as % change from mean value was not significantly different between SHR and WKY. By computer techniques the correlation between HR, MAP and SNA could be calculated during spontaneous variations of these parameters. The slope of the regression line correlating HR and SNA was significantly steeper in SHR than in WKY (0.73, 0.47 resp.). Thus a certain change in HR was associated by a greater change in SNA in SHR compared with WKY. Spontaneous changes in SNA could be divided in principally two different patterns. One typical pattern was a rise in SNA in parallel with a drop in MAP. This pattern was most likely triggered by the arterial baroreceptors and was called a "baroreceptor-pattern". Marked spontaneous excitations in SNA and HR was also observed during natural behaviours such as eating, drinking and explorative behaviour, a so called "centrally mediated pattern".     

GLP-1受体激动剂Exenatide改善糖尿病大鼠心血管功能

目的 探讨胰高血糖素样肽1(GLP-1)受体激动剂Exenatide (Ex)治疗对糖尿病大鼠心血管功能的影响,为其临床应用提供实验依据.方法 用单因素四水平不等重复的完全随机实验进行研究,34只Wistar大鼠随机分成4组:对照组(C,n=7),糖尿病组(DM,n=9),小剂量Ex治疗组(Emin,n=9),大剂量Ex治疗组(Emax,n=9).检测大鼠空腹血糖水平;使用小动物超声仪观察大鼠左心室射血分数(EF)、左心室短轴缩短率(FS);观察腹主动脉血流速(AF),胸主动脉内膜扫描电镜观察血管内膜损伤.结果 DM组空腹血糖明显升高(P＜0.01),Exenatide治疗组空腹血糖较DM组显著降低(P＜0.05).DM组EF、FS较对照明显降低(P＜0.01),Exenatide治疗组EF、FS明显升高(P＜0.05).DM组腹主动脉血流速明显降低(P＜0.01),血管内膜出现明显损伤;Exenatide治疗组腹主动脉血流速较DM组明显升高(分别P＜0.05,P＜0.01),血管内膜损伤减轻.结论 Exenatide能够降低糖尿病大鼠血糖水平,并改善糖尿病心脏和血管功能.