Both plasma and renal endothelin-1 participate in the acute cardiovascular response to exercise

Plasma endothelin (ET-1) and renal endothelin are two distinct functional systems involved in maintaining blood volume. To investigate whether plasma and renal ET-1 participate in the cardiovascular response to exercise-induced hypovolaemia, we studied changes in plasma and urinary ET-1 in healthy non-professional athletes after 2 h of jogging performed both without and with drinking isotonic fluids. After the run, which caused a 13% plasma volume (PV) reduction, plasma and renal ET-1 (+117% and +118%) increased significantly (all P  < 0.01). Fluid loss restitution during the run significantly attenuated either the PV contraction (−1.2%) and plasma and renal ET-1 increase (+2 and +3%). At multiple regression analysis changes in AVP plasma concentration, and not in PRA or PV per se , were significantly related to ET-1 changes both in plasma and urine. The present findings indicate that both plasma and renal ET-1 participate in the cardiovascular response to hypovolaemia induced by long-lasting, dynamic exercise.     

Relationship between plasma endothelin-1 concentration and cardiovascular responses during high-intensity eccentric and concentric exercise

The present study investigates the relationship between plasma endothelin-1 (ET-1) concentrations and cardiovascular responses during eccentric (ECC) and concentric (CON) resistance exercises. Eight healthy males (aged 24.3 +/- 1.2 years) performed dynamic forearm exercises for 60 s at an angular velocity of 60 masculine s(-1). Each test comprised 60-s high-intensity (80% of peak torque) bouts of randomly selected ECC and CON contractions, and the plasma ET-1 concentrations were measured before and after each type of contraction. Systolic pressure (SBP), diastolic pressure (DBP), pulse pressure and heart rate (HR) during ECC and CON contraction were also measured. Mean arterial pressure (MAP) was calculated from SBP and DBP. The rate-pressure product (RPP) was calculated from SBP and HR. The plasma ET-1 concentration was significantly increased after CON, compared with ECC contraction (P<0.01). Moreover, SBP, DBP, MAP and RPP were significantly increased (P<0.05, P<0.01, P<0.001, respectively) during CON, compared with ECC contraction. Correlations between plasma ET-1 concentration and MAP were not significant during ECC contraction, but significantly positive during CON contraction (P<0.05). These results showed that CON contraction is associated with ET-1 production and a greater increase in blood pressure compared with ECC contraction.     

Pituitary-adrenal response to static exercise in man.

1. Changes in plasma concentrations of catecholamines and cortisol were measured before and after static exercise performed by the subject pushing with both legs against a strain-gauge bar. No marked changes in plasma catecholamine were observed but plasma cortisol increased after the subject pushed for 3 min at 50% of maximum force. 2. Holding a 20 kg weight for 5 min in one hand caused a rise in plasma cortisol and in plasma ACTH but no changes in growth hormone were observed.     

Arterial and venous plasma catecholamines during submaximal steady-state exercise

Arterial and venous plasma catecholamine responses to 15 min of cycling at 60% of maximal oxygen uptake were examined 11 times during exercise and recovery in nine young men. Intra-arterial blood pressure, heart rate and oxygen uptake were recorded continuously. All variables increased significantly during the initial 4 min, after which oxygen uptake, diastolic blood pressure and arterial plasma adrenaline showed no further increase. Heart rate and plasma noradrenaline, however, continued to increase, although significantly more slowly, and were closely correlated (r = 0·81, 95% CI 0·71–0·87), as were systolic blood pressure and heart rate (r = 0·78, 95% CI 0·71–0·87). Venous plasma adrenaline showed a steady increase during the whole exercise period and thus a different response pattern from arterial plasma adrenaline. In conclusion, arterial plasma catecholamines respond to steady-state exercise by a two-phase pattern paralleling the changes in arterial blood pressure and heart rate. Venous sampling does not reveal this association.     

Plasma endothelin-1 during central hypovolaemia in man

Summary. Endothelin-1 (ET-1) is a potent vasoconstricting peptide with effect on resistance as well as capacitance vessels. We followed ET-1 in arterial plasma together with heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and thoracic electrical impedance (TI) in seven men during central hypovolaemia induced by 50± head-up tilt. During tilting plasma ET-1 increased from 1.1 ±0.2 to 1.4 ± 0.3 pmol 1^-1 (mean ± SE) concomitant with an increase in total peripheral resistance (TPR) (from 15 ± 2 to 25 ± 3 mmHg min 1^-1) (P< 001), and HR (from 67 ± 2 to 94 ± 5 beats min^-1) (P<0.01) while MAP remained unchanged. CVP decreased (from 1.8±0.9 to -1.6±1.0 mmHg) (P<0.01) during tilting and remained unchanged during sustained tilt despite further reduction of central blood volume as recorded by TI. Presyncopal symptoms occurred after 28 ± 6 min associated with decreases in HR (to 70 ± 6 beats min^-1), MAP (from 90 ± 3 to 52 ± 4 mmHg) and TPR (to 11 ± 2 mmHg min l^-1) (P<0.01). At this time plasma ET-1 reached its highest level of 1.6±0.3 pmol l^-1 (P<0.01). Data show that head-up tilt is associated with increased plasma concentrations of ET-1 which may play a role in maintaining vascular tone in situations with a reduced central blood volume.     

Hypertensive left ventricular hypertrophy is linked to an enhanced catecholamine response to submaximal exercise.

BACKGROUND: The serial plasma catecholamine response to exercise has not been studied fully in relation to left ventricular hypertrophy (LVH) in patients with hypertension (HT). This study determined whether plasma catecholamine responses to exercise are altered in essential HT in the presence or absence of LVH. MATERIALS AND METHODS: Plasma noradrenaline (NA) and plasma adrenaline (A) were measured at rest, during and after treadmill exercise in 59 hypertensive subjects and 22 age-matched control subjects. Patients were divided into LVH(-) (n = 20) and LVH(+) (n = 39) stratified by left ventricular mass index [LVMI: control subjects, LVH(-), LVH(+): 114 +/- 4, 105 +/- 3, 151 +/- 3 g m-2]. RESULTS: Exercise time (9.9 +/- 0.6, 7.6 +/- 0.7, 7.3 +/- 0.6 min) was shorter in patients with HT. Both systolic and diastolic blood pressures were higher in patients with HT, and no difference was observed between LVH(-) and LVH(+) patients. Resting plasma NA was not different (157 +/- 16, 173 +/- 17, 167 +/- 14 pg mL-1), but plasma NA at stage I (300 +/- 30, 342 +/- 40, 469 +/- 40 pg mL-1) was higher in LVH(+) patients than in LVH(-) patients or control subjects. Plasma A response to exercise was similar among the three groups. There was a positive correlation (r = 0.38, P < 0.001) between LVMI and Deltaplasma NA at stage I in all subjects. CONCLUSIONS: Patients with essential HT with LVH had augmented plasma NA response during submaximal exercise, whereas patients without LVH did not exhibit this augmentation. The positive correlation between LVMI and Deltaplasma NA suggested a possible association between the degree of cardiac hypertrophy and sympathetic activation during exercise.     

Endothelin-1 urinary excretion, but not endothelin-1 plasma concentration, is increased in renovascular hypertension.

Animal experiments have shown an increase in prepro-endothelin-1 (prepro-ET-1) mRNA expression in the clipped kidney but none in the aortic and mesenteric arteries in 2-kidney, 1-clip Goldblatt hypertensive rats. The present study was aimed at investigating whether plasma and renal endothelin-1 (ET-1) systems are differently activated in patients with renovascular hypertension (RH). The plasma concentration and urinary excretion of ET-1 were measured in 5 patients with RH (before and after successful renal angioplasty), in 7 patients with essential hypertension (EH), and in 8 normotensive control subjects. Immediately before renal angioplasty, plasma samples for ET-1 and plasma renin activity (PRA) measurements were withdrawn from the aorta and both renal veins. Unlike the PRA, the plasma ET-1 concentration did not significantly differ between the involved and the uninvolved sides. The urinary ET-1 excretion level (Fig 1) was markedly increased in patients with RH (30+/-4 ng/g urinary creatinine (UC) vs. 2.5+/-0.2 ng/g UC and 2.6+/-0.5 ng/g UC in control subjects and patients with EH, respectively; P<.001), whereas the plasma ET-1 concentration was normal (0.8+/-0.2 pg/mL vs. 0.65+/-0.3 pg/mL and 0.8+/-0.2 pg/mL in control subjects and EH, respectively, not significant). Renal angioplasty was followed in all patients by normalization of blood pressure and PRA. One week after angioplasty, urinary ET-1 decreased to one fourth of baseline (8.04+/-5.23 ng/g UC, P<.001 vs. values before angioplasty and P<.04 vs. control subjects) and normalized 1 month thereafter (3.13+/-1.62 ng/g UC, not significant vs. control subjects), whereas plasma ET-1 remained steady. The present findings clearly indicate that in patients with RH, urinary ET-1 excretion is increased, whereas plasma ET-1 concentration remains normal. Successful percutaneous transluminal renal angioplasty induced a notable reduction in ET-1 urinary excretion, whereas it did not affect ET-1 plasma concentration.     

Effects of endothelin-1 on circulating adhesion molecules in man

Several studies point to a role for endothelin-1 (ET-1) in enhancing adhesion molecule expression and leucocyte adhesion. We thus hypothesized that ET-1 would induce expression of adhesion molecules by endothelial cells and by leucocytes in humans, and hence compared with placebo the effect of a continuous 6-h ET-1 infusion on plasma levels of circulating (c)E-selectin, cP-selectin, intercellular and vascular cell adhesion molecule 1. In addition, we investigated the effects of ET-1 on expression of the leucocyte adhesion molecules CD11b/CD18 and L-selectin on monocytes and neutrophils. After an open pilot study to evaluate the safety of a 6-h ET-1 infusion of 0.4 pmol kg⁻¹ min⁻¹ ( n  = 4), the main study was conducted as a randomized, double-blind, two-way, cross-over trial in 12 additional young healthy male volunteers, who received the same treatment and were observed over a period of 24 h. ET-1 infusion decreased renal plasma flow by 43% (CI 35–51%; P  < 0.001) and increased the filtration fraction by 80% (CI 20–110%; P  < 0.001). Heart rate decreased by −10% (CI −4% to −15%) at 6 h under ET-1 infusion in the cross-over trial ( P  = 0.012 between periods). Although ET-1 infusions increased plasma levels of ET-1 by about 300%, ET-1 elicited no relevant changes in any circulating adhesion molecules or leucocyte adhesion molecules measured. In the placebo period small diurnal changes were observed for cP-selectin (–8%, CI −14 to −3%, P  = 0.008) and cE-selectin (–6%, CI −10 to −3%, P  = 0.003) at 12 h (20.45 h). In sum, ET-1 does not regulate circulating adhesion molecules in healthy men. Circadian variations may exist for plasma levels of cP-selectin and cE-selectin.     

一次性急性力竭运动后大鼠血浆内皮素、肾上腺髓质素、降钙素基因相关肽含量的变化

目的:观察一次急性力竭运动对机体心血管系统内分泌的影响。方法:实验于2004-05在扬州大学体育学院运动人体科学研究所实验动物中心和苏北人民医院生化检测中心放免实验室完成。①20只雄性SD大鼠按编号随机分成一次急性力竭和对照组2组,每组10只,一次力竭组大鼠做一次急性力竭游泳运动,力竭判断标准按Thomas等报道文献的标准。对照组:常规饲养,不加干预。②大鼠力竭后立即从腹主动脉处取血2mL,注入预置含100g/L乙二胺四乙酸二钠30μL和抑肽酶40μL的玻璃试管中,混匀。所有血液标本立即低温(4℃,3000r/min,10min)分离血浆,暂存于4℃冰箱内,并在24h内采用放射免疫法,测定内皮素、肾上腺髓质素及降钙素基因相关肽含量。结果:一次急性力竭组取血前死亡2只,进入结果分析18只。①一次性力竭组大鼠血浆内皮素含量比对照组升高了22.11%[(176.62±13.62),(144.64±14.30)ng/L],差异显著(P<0.05)。②一次性力竭组大鼠血浆肾上腺髓质素含量比对照组升高了6.14%[(254.55±34.72),(239.83±34.10)ng/L],差异不显著(P>0.05)。③一次性力竭组大鼠血浆降钙素基因相关肽含量比对照组下降了46.03%[(90.95±24.39),(168.52±32.23)ng/L,差异显著(P<0.05)]。结论:一次急性力竭运动会导致血管活性肽的分泌严重失衡。     

Arterial plasma potassium measured continuously during exercise in man

Five continuous records of arterial plasma potassium were obtained from three normal subjects during brief periods (5-7 min) of exercise (100 W). In two of these subjects hepatic venous blood samples were withdrawn at 0.5-1.0 min intervals and analysed in vitro for plasma potassium. Arterial plasma potassium rose rapidly at the start of exercise from 3.8 +/- 0.3 mmol/l (mean +/- SD) to plateau levels of 5.4 +/- 0.1 mmol/l. One of the above subjects and a further subject were studied after beta-blockade with propranolol. This resulted in an exaggerated rise in arterial plasma potassium during exercise. Hepatic venous potassium measurements indicated that the liver probably had little effect on potassium changes during exercise. The changes in arterial plasma potassium during exercise are rapid and substantial. If transmitted to the extracellular fluid these changes would alter cell transmembrane potential and might as a result alter receptor sensitivity.     

Is hypercapnia necessary for the ventilatory response to exercise in man?

1. Continuous recordings of arterial pH, ventilation, airway CO2 and heart rate were made during rest and during 3-4 min periods of rhythmic leg exercise in four renal patients with arteriovenous shunts. 2. The patients were anaemic (haemoglobin 6.5-9.0 g/dl) but had a normal ventilatory response to exercise as judged by the ratio of the change in ventilation to the change in CO2 production. 3. Breath-by-breath oscillations in arterial pH disappeared for the majority of the exercise period in each patient. 4. Changes in mean arterial pH and end-tidal CO2 tension with exercise were inconsistent between subjects but consistent within a given subject. On average, mean arterial pH rose by 0.011 pH unit. Changes in end-tidal CO2 tension reflected changes in mean pHa by falling on average by 1 mmHg (0.13 kPa). 5. Hypercapnia and acidaemia were not found to be necessary for the ventilatory response to moderate exercise.     

Potentiated hepatic microcirculatory response to endothelin-1 during polymicrobial sepsis

We conducted this study to elucidate the role of endothelins (ET-1) in mediating the hepatic microcirculatory dysfunction observed in response to sepsis. Following 24 h of cecal ligation and puncture (CLP), we performed intravital microscopy both in vivo and on isolated perfused livers. Portal resistance increased in response to ET-1 in both sham and septic rats, with no significant difference between the two in either in vivo or in isolated livers. Sinusoidal volumetric flow (Qs) was evaluated using red blood cell velocity (V(RBC)) and sinusoidal diameter (Ds) to determine microvascular hemodynamic integrity. Qs decreased in response to ET-1 in livers from CLP rats compared with sham (P < 0.05, CLP vs. sham) in both in vivo and isolated livers. In vivo infusion of ET-1 resulted in greater constriction of sinusoids in the CLP group compared with sham (P < 0.05), resulting in higher sinusoidal resistance. Microvascular hyper-responsiveness was accompanied by hepatocellular injury in CLP rats, but not in sham rats. RT-PCR was performed to measure mRNA levels of ET-1, its receptors ET(A) and ET(B), inducible and constitutive nitric oxide (NO) synthase (iNOS and eNOS, respectively), and heme oxygenase 1 (HO-1). After CLP, both ET-1 and ET(B) mRNA increased, whereas ET(A) mRNA tended to decrease, although the change was not statistically significant. Livers from CLP rats showed no significant change in levels of eNOS mRNA, but showed a significant increase in iNOS expression (13.5-fold over sham). There was no change in the level of HO-1 mRNA between sham and CLP groups. Taken together, these results suggest that sepsis sensitizes the hepatic microcirculation to ET-1. More importantly, an impaired microcirculatory flow due to ET-1 in sepsis contributes to hepatic injury. Further, localized imbalances between endothelins and NO may mediate the altered microvascular response during sepsis.     

血浆MMP-9与体外循环炎性反应相关性研究

目的 :探讨体外循环 (CPB)围术期血浆基质金属蛋白酶 9(MMP 9)和细胞因子之间的关系。方法 :选择 3 0例接受CPB的病人 ,分别在CPB开始前、开始后 3 0min、结束时、结束后 2h采集血标本 ,采用酶联免疫吸附分析方法检测血浆MMP 9和TNF α、IL 8、IL 6的浓度。结果 :(1)血浆MMP 9和TNF α、IL 8的浓度在CPB期间呈逐渐升高 ,在CPB结束时达到最高峰值 ,之后呈下降趋势 ,IL 6在CPB结束后仍继续升高。 (2 )围CPB期血浆MMP 9与TNF α、IL 8、IL 6之间均呈明显的正相关性。结论 :CPB期间血浆MMP 9、TNF α、IL 8、IL 6释放均明显增加 ,除IL 6外在CPB结束时达到最高峰值 ,围CPB期细胞因子可以诱导MMP 9的激活和释放 ,同时MMP 9可以通过对细胞因子的正反馈作用而参与CPB过程的炎症反应。     

Effect of marihuana on cardiorespiratory responses to submaximal exercise.

Six male chronic marihuana (MH) users exercised on a bicycle ergometer for 15 min at approximately 50% VO2max under 3 conditions: (1) not smoking (control), (2) after smoking MH containing 7.5 mg (-) delta-9-tetrahydrocannabinol, and (3) after smoking placebo marihuana (PL). The MH was administered double-blind in a counterbalanced repeated-measures design. Heart rates (HRs), arterial blood pressures (BPs), pulmonary ventilation (VE), and oxygen uptake (VO2) were measured during exercise and 15 min recovery. PL had no effect on any of the physiologic variables. Smoking MH had no effect on systolic blood pressure (SBP), diastolic blood pressure (DBP), VE, or VO2, but did induce a marked increase in heart rate which persisted throughout exercise and recovery periods, averaging 34% higher than control values at rest, 18% higher during exercise, and up to 50% higher during recovery. MH smoking increased the product of HR x SBP in all circumstances.     

Relationship between plasma sodium concentration and vascular reactivity in man

Experiments were done to study the effects of acute changes in plasma sodium concentration [Na] on vasoconstrictor responses to norepinephrine and to reflex sympathetic stimulation in man. [Na] in the venous return from the forearm of each of 21 normal subjects was reduced (to an average of 118 mEq/liter), increased (147 mEq/liter), and maintained within the normal range (140 mEq/liter) by means of infusions into the brachial artery of three solutions containing different [Na]. Mannitol or sucrose and disodium sulfate were substituted for sodium chloride to produce the desired changes in [Na] without changing blood osmolarity.     

Decrease of plasma fibronectin concentration following infusion of a gelatin-based plasma substitute in man

Intravenous infusion of 500 ml of a gelatin-based plasma substitute, Haemaccel, given to healthy volunteers, resulted in a significant decrease of the immunoreactive plasma fibronectin concentration 48 h and 72 h after infusion. One hour after infusion, the ability of fibronectin to bind gelatin was inhibited with a gradual recovery within 48 h. A dextran based plasma substitute, Macrodex, did not have this effect on plasma fibronectin.