Erythrocyte Na+–H+ exchanger kinetics and Na+–Li+ countertransport activity in essential hypertensive patients

The authors measured Na⁺–H⁺ exchanger kinetics together with Na⁺–Li⁺ countertransport V _max in the erythrocytes of 21 subjects with essential hypertension and 16 normotensive control subjects. Na⁺–H⁺ exchanger V _max appeared to be increased in patients with essential hypertension, while the Na⁺–H⁺ exchanger affinity for intracellular proton sites ( K _50%) proved to be unchanged and the index of cooperativity among intracellular proton binding sites as measured by Hill's coefficient (Hill's n ) decreased as compared with normotensive control subjects. Na⁺–Li⁺ countertransport V _max appeared to be higher in patients with essential hypertension than in control subjects. The authors were unable to find any correlations between Na⁺–H⁺ exchanger kinetic parameters and metabolic variables such as parameters of insulin resistance and plasma lipids. On the basis of the data obtained, erythrocyte Na⁺–H⁺ exchanger activity was found to be abnormal in two kinetic variables in essential hypertensive patients and showed no simple linear correlations with the main variables of glucose metabolism, plasma lipids, renin or aldosterone.     

Abnormal Na+K+ cotransport function in a group of patients with essential hypertension

In 50 normotensive controls, the increase in erythrocyte Na+ concentration up to 12.4 +/- 2.0 mmol/l cells (mean +/- SD) ensures half-maximal stimulation of outward Na+,K+ cotransport fluxes. Forty-six out of sixty-five patients with essential hypertension required more than 16 mmol/l cells of internal Na+ concentration to obtain a similar effect, strongly suggesting an abnormal cotransport function. Seven out of fourteen hypertensive patients with normal Na,K cotransport function showed Na+,Li+ countertransport fluxes higher than the normal upper limit of 220 mumol (1 cells h)-1. Conversely, countertransport fluxes were normal in fourteen hypertensives with abnormal cotransport function. The above results indicate that the total population of patients with essential hypertension is heterogeneous and includes one subgroup of subjects with abnormal Na+,K+ cotransport function, and another with increased Na+,Li+ countertransport fluxes.     

The lymphocyte Na+/H+ antiport: activation in primary hypertension and during chronic NaCl-loading

Abstract. Increased activity of the Na⁺/H⁺ antiport may be a major abnormality in essential hypertension. The activity of this transport system was investigated in lymphocytes from 13 patients with untreated essential hypertension (Ht) and 13 normotensive control subjects (Nt) on an ad libitum (130–170 mmol d^-1) NaCl intake. Furthermore, the effects of different states of NaCl balance on lymphocyte Na⁺/H⁺ antiport were evaluated in two groups of Nt volunteers receiving 20 vs. 300 mmol d^-1 (n= 8) and 85 vs. 200 mmol d^-1 (n= 14) of NaCl for 1 week each and in seven Ht patients (20 vs. 300 mmol NaCl d^-1 for 1 week each). Additionally, during the 20 and 300 mmol/d NaCl intake red blood cell membrane transport was studied in eight subjects. For the determination of lymphocyte antiport activity, cells were loaded with the cytosolic pH (pH_i) indicator bis-carboxyethyl carboxyfluorescein (BCECF-AM) and acidified by addition of different amounts of Na⁺-propionate (5–40 mM). Initial pH_i-recovery was taken as the activity of the antiport system and plotted against pH_i-values after acidification. Non-linear regression analysis yielded higher ’apparent’ maximal transport rates in Ht than Nt (Nt: 2·00 pL 0·22; Ht: (3·81 pL 0·59)·10^-3 s^-1; P < 0·025). In contrast, baseline pH_i-values and pH_i-values at half-maximal activity (pK) were identical in Nt and Ht. In normotensive control subjects on an NaCl intake of 20, 85, 200 and 300 mmol d^-1 for 7 d, ’apparent’ maximal transport rates averaged 2.75 0·20, 2·89 0·17, 2·81 ± 0·18 and (3·62 ± 0·25) · 10^-3 s^-1, respectively. Thus, antiport activity was significantly (P < 0·05) stimulated on the 300 mmol d^-1 intake as compared to the three other NaCl intakes. The extreme intakes of NaCl (20 vs. 300 mmol d^-1) in normotensive volunteers did not affect the erythrocyte Na⁺/K⁺ pump, Na⁺/K⁺ cotransport and Na⁺/Li⁺ countertransport. Our study supports the concept that a group of patients with primary hypertension exhibit an activated Na⁺/H⁺ antiport. Furthermore, our data demonstrate that a chronic high intake of NaCl is associated with an increase in lymphocyte antiport activity towards the high values observed in primary hypertension.     

Abnormal Na+-K+ ATPase kinetics in a subset of essential hypertensive patients

We have performed a kinetic analysis of the interaction of Na+-K+ ATPase with internal Na+ in erythrocytes of 30 normotensive controls and 72 essential hypertensive patients. Neither the maximal rate of ouabain-sensitive sodium efflux (Vmax) nor the internal Na+ content required for half-maximal stimulation (K50%) were significantly different between normotensive and hypertensive patients. Nevertheless, using the 95% confidence limits of the K50% in the normotensive group as a cut-off point, 13 (18.06%) essential hypertensive patients exhibited increased values of this parameter (29.16 +/- 4.31 mmol l-1 cells) revealing decreased affinity of Na+-K+ ATPase for internal Na+ (Pump-hypertensives). The Vmax was also higher in the Pump '-' subset (14.08 +/- 4.85 mmol (1 cells h)-1 vs. 6.92 +/- 1.80; P = 0.0002) and 10 of these 13 hypertensives exhibited a Vmax above the upper end limit of 10.5 mmol (1 cells h)-1, suggesting a compensatory effect. No differences were observed between the Pump '-' subset and the remaining 59 hypertensives without Na+-K+ pump abnormality when basal erythrocyte Na+ content and clinical parameters of hypertension were examined. Decreased apparent affinity of Na+-K+ pump for internal Na+ present in 9-27% of essential hypertensives may be implicated in pathogenetic mechanisms of hypertension.     

Local and systemic effects of Na+/K+ ATPase inhibition

The positive inotropic and electrophysiological effects of cardiac glycosides on cardiac muscle are mediated through inhibition of Na⁺/K⁺ ATPase by binding to a specific extracytoplasmic site of the a-subunit of this enzyme. The inhibition of Na⁺/K⁺ ATPase affects ionic flux and produces direct local effects on cardiac contractility, electrical excitability and conduction, but also profound systemic effects mainly as a result of haemodynamic changes. These effects are responsible for beneficial therapeutic as well as toxic effects.
Inhibition of Na⁺/K⁺ ATPase results in potentiation of K⁺ loss from cells and Na⁺ entry into cells, so consequently affects action potential generation and propagation. This also underlines the potentiation of certain effects of cardiac glycosides by hypokalemia and hypomagnesaemia, and the effects of changes in calcium homeostasis on the cardiac glycoside pharmacodynamics. Furthermore, inhibition of Na⁺/Ca⁺⁺ exchange enhances Ca⁺⁺ mobilization and promotes contractility. These effects (locally and systemically) differ greatly, depending on the haemodynamic status and myocardial oxygen supply.
Cardiac glycosides have less affinity for Na⁺/K⁺ ATPases at other sites (e.g. skeletal muscle), but some extracardiac effects (vascular effects, effects on colour vision, CNS and autonomic effects, renal effects) may be related to Na⁺/K⁺ ATPase inhibition.     

Na+/H+ antiporter activity in peripheral blood lymphocytes of obese and type 2 diabetic patients is increased only in the presence of arterial hypertension

Abstract. The aim of this work is to evaluate whether type 2 diabetes mellitus, obesity and arterial hypertension, three conditions characterized by the presence of insulin resistance, share some common genetic markers. A potential candidate is the Na⁺/H⁺ anti-porter, the increased activity of which is considered a marker of essential hypertension. This ion exchanger seems to be related to the Na⁺/Li⁺ countertransport, that is considered a marker of insulin resistance in essential hypertension and in type 1 diabetes mellitus. In this study we wished to clarify whether the activity of the Na⁺/H⁺ antiporter is increased not only in hypertensive subjects, but also in obese and type 2 diabetic patients, both in the presence and in the absence of arterial hypertension. The activity of the ion exchanger was measured in peripheral blood lymphocytes (PBL) by clamping intracellular pH (pH_i) at 5·8–6·2 and then detecting the rate of the proton efflux after sodium addition. In the absence of arterial hypertension, no significant difference in this parameter was observed in obese and type 2 diabetic patients in comparison with normal subjects. In the presence of arterial hypertension, there was a significant increase in the Na⁺-induced H⁺ efflux at the internal pH (pHi) values of 5·8 and 6·2 both in hypertensive controls and in hypertensive obese and type 2 diabetic patients (P= 0·05–0·0001 vs. normotensive subjects and patients). In particular, H⁺ efflux at pH 5·8 (mmol l^-1 min^-1) was 35·36 ± 2·48 in normotensive and 42·77 ± 1·63 in hypertensive control subjects (P= 0·045), 33·06 ± 1·88 in normotensive and 50·40 ± 5·21 in hypertensive obese patients (P= 0·009), 31·16 ± 1·84 in normotensive and 55·54 ± 5·83 in hypertensive type 2 diabetic patients (P= 0·0001). H⁺ efflux showed a significant correlation with both systolic (at pHi 5·8, r = 0·473, P= 0·001; at pHi 6·2, r = 0·357, P= 0·016) and diastolic blood pressure (at pHi 5·8, r = 0·600, P= 0·0001; at pHi 6·2, r = 0·555, P= 0·0001). Therefore, our study demonstrates that the hyperactivity of the Na⁺/H⁺ exchanger in peripheral blood lymphocytes is also a marker of arterial hypertension in obesity and in type 2 diabetes mellitus, and that the exchanger activity is not increased in these two conditions in the absence of arterial hypertension.     

Erythrocyte Na+-H+ exchanger and Na+-Li+ countertransport activity in primary aldosteronism

Abstract. Several authors have described increased Na-H exchanger activity in essential hypertension but no data are available in secondary forms of hypertension such as primary aldosteronism. We measured Na-H exchanger kinetics together with Na-Li countertransport V _max in the erythrocytes of eight patients with primary aldosteronism and in 15 normotensive control subjects. Plasma aldosterone, plasma renin and plasma potassium were also evaluated. Na-H exchanger V _max appear to be increased in patients with primary aldosteronism and Hill's n , an index of co-operativity amongst intracellular proton binding sites, was significantly lower in patients than in controls. No statistically significant differences were found between affinity for intracellular protons (K50%) and for Na-Li countertransport V _max between the two groups studied. We were unable to find any correlations between Na-H exchanger V _max and Na-Li countertransport V _max in the two groups considered as a whole. From the present data Na-H exchanger overactivity would not appear to be a specific feature of essential hypertension but seems to be characteristic in patients with primary aldosteronism.     

Erythrocyte Li+/Na+ and Na+/H+ exchange, cardiac anatomy and function in insulin-dependent diabetics

It has been proposed that an increased activity of cell membrane Na+/H+ exchange, mirrored by increased erythrocyte Li+/Na+ exchange, may facilitate cell hypertrophy and hyperplasia. Patients with insulin-dependent diabetes mellitus may develop a specific cardiomyopathy with systolic and diastolic abnormalities and increased thickness of the left ventricle. Therefore, we have investigated the relationships between erythrocyte Li+/Na+ and Na+/H+ exchange and echocardiographic parameters in 31 male insulin-dependent diabetics (aged 17-68), in good metabolic control. Three had untreated mild hypertension. In all patients the urinary albumin excretion rate was less than 200 micrograms min-1. Ten patients had a Li+/Na+ countertransport higher than 0.37 mmol l-1 cell h-1, the upper normal limit for our laboratory (0.49 +/- 0.10, mean +/- SD). In comparison with the patients with normal countertransport, they had increased interventricular septum thickness and relative wall thickness (h/r). End diastolic volume and cardiac index were reduced while blood pressure and urinary albumin excretion rate were similar. In the whole study group, interventricular septum thickness was significantly correlated to Li+/Na+ exchange (r = 0.61, P less than 0.001) and Na+/H+ exchange (r = 0.35, P less than 0.05), independently of the effect of age and blood pressure. Posterior wall thickness was correlated to Li+/Na+ exchange (r = 0.38, P less than 0.05) and h/r to Li+/Na+ exchange (r = 0.41, P less than 0.05) and to Na+/H+ exchange (r = 0.44, P less than 0.05). Li+/Na+ exchange was negatively correlated to cardiac index (r = -0.37, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute saline infusion induces extracellular acidification and activation of the Na+/H+ exchanger in man

The effect of acute expansion of the extracellular fluid volume (ECV) with isotonic (0.9%) saline on the activity of the lymphocyte Na⁺/H⁺ antiport (NHE) was studied in a total of 18 healthy volunteers. Saline was infused at a constant rate so that 4 mmol kg^?1 b.w. was administered over 2 h. NHE activity was measured by quantifying cytosolic pH (pH_i) recovery following acidification of the cells with propionic acid and by pH clamping at various pH_i values between 7.2 and 5.8 using nigericin. Both methods demonstrate NHE activation associated with intravenous saline infusion, the kinetic difference being a marked decrease in the Hill coefficient n from 3.28 ± 0.21 (SEM) to 2.22 ± 0.11 in the absence of changes in baseline pH_i (7.14 ± 0.02 vs. 7.08 ± 0.02; P = 0.15), V_max (42.8 ± 2.7 vs. 48.1 ± 2.8 mmol L^?1 min^?1; P = 0.08) and pK (6.32 ± 0.04 vs. 6.35 ± 0.02). NHE activation was associated with significant decreases in serum chloride (P = 0.016), calcium (P = 0.008), total cholesterol (P = 0.008), low-density lipoproteins (P = 0.016) and high-density lipoproteins (P = 0.008). Moreover, saline infusion induced extracellular acidification with a decrease in pH from 7.39 ± 0.01 to 7.37 ± 0.01 (P = 0.016), HCO₃^? from 23.3 ± 0.43 mmol L^?1 to 21.3 ± 0.25 mmol L^?1 (P = 0.008) and base excess from ?1.03 ± 0.38 mmol L^?1 to ?3.00 ± 0.31 mmol L^?1 (P = 0.008). Our results show for the first time that acute ECV expansion with isotonic saline is followed by an activation of the lymphocyte NHE. The underlying mechanism(s) remain to be investigated. However, the demonstration in our study of marked changes in acid–base balance induced by acute saline points to a possible inter-relationship of antiporter activation and extracellular acidification.     

Effect of inhibition of the electrogenic Na+/K+ pump on the mechanical activity in the rat uterus

Summary— The effects of ouabain and K⁺-free solution were studied in estrogen-primed rat uterine strips under resting tone or repeatedly stimulated with KCl, acetylcholine or oxytocin applied for 20 minutes at 60 minute intervals. These effects were compared with those of the K⁺ channel opener cromakalim. In preparations under resting tone, ouabain (0.1 mM and 0.3 mM) induced rhythmic contractions which disappeared after 20–30 minutes whereas at a higher concentration (1 mM) it evoked a rapid, phasic response followed by a small tonic contraction. Exposure of the strip to a K⁺-free solution induced either rhythmic waves, which ceased after 8–10 minutes, or a single phasic contraction which was followed by a small and slow increase in the resting tone (54 ± 10 mg after 180 min exposure). Nifedipine (0.3 μM) abolished the rhythmic or phasic component of these responses but failed to modify the late small tonic contraction induced by ouabain 1 mM or by K⁺-free solution. Ouabain (0.1–1 mM) or K⁺-free-evoked responses disappeared after short (4 min) or prolonged (60 min) exposure to a Ca²⁺-free, 3 mM EGTA-containing solution. Cromakalim (10 nM ?0.1 mM) did not induce any variation in the resting tone either in the presence or in the absence of Ca²⁺ in the medium. In strips repeatedly stimulated with acetylcholine (0.1 mM) or oxytocin (1 μM), ouabain (0.3 mM), K⁺-free-solution and cromakalim (10 μM) reduced the amplitude of the initial, phasic response and progressively decreased the oscillatory component of the response to these agonists. Conversely, the successive responses evoked by KCl 60 mM in similar experimental conditions were not affected by ouabain or cromakalim. Ouabain (0.3 mM), K⁺-free solution and cromakalim (10 μM) decreased the Ca²⁺-independent, maintained contractions induced by acetylcholine or oxytocin after prolonged exposure to a Ca²⁺-free, EGTA-containing medium. These inhibitory effects were partially or completely reversed in the presence of the non-selective potassium channel blocker tetraethylammonium (10 mM) or in a Ca²⁺-free solution containing 60 mM K⁺. In conclusion, these results suggest that the response induced by ouabain or K⁺-free solution in estrogen-primed rat myometrium involves Ca²⁺ influx through potential-operated calcium channels but not Ca²⁺ release from intracellular stores. In addition, our results show that prolonged exposure to ouabain or K⁺-free medium decreases membrane receptor-mediated responses in rat uterus. This inhibitory effect seems to be the result, at least in part, of a decrease in the cytosolic level of K⁺, due to the inhibition of the electrogenic Na⁺ pump.     

A single isoform of the Na+/K+-ATPase α-subunit in Diptera: evidence from characterization of the first extracellular domain

The first extracellular domain of the α-subunit of the Na⁺/K⁺-ATPase (sodium/potassium pump) is functionally important, affecting sensitivity of the enzyme to cardiac glycosides (e.g. ouabain) and being implicated in the transport of K⁺. This domain is also variable among mammalian isoforms of the α-subunit. Using PCR, we have isolated from seven insect species with contrasting physiologies a DNA fragment containing this region, in order to help determine whether tissue-specific expression might be associated with isoforms encoded by a gene family, as it is in mammals. A single sequence (with one ORF) characteristic of Na⁺/K⁺-ATPase was obtained from genomic DNA of each species. Only the fragment from Manduca sexta contained an intron, but at a location different to that found in mammals. For all Diptera so far characterized, the species phylogeny is the same as the α-subunit gene phylogeny (based on the sequences of the first extracellular domain and flanking transmembrane domains). The results strongly indicate a single, ouabain-sensitive isoform of the α-subunit of Na⁺/K⁺-ATPase is present in Diptera.     

Role of Na+-H+ Exchange on Reperfusion Related Myocardial Injury and Arrhythmias in an Open-Chest Swine Model

The inhibition of Na⁺-H⁺ exchange (NHE) with amiloride analogues in vitro has been shown to prevent reperfusion arrhythmias and additional cell necrosis. Inhibition of intracellular Ca²⁺ overload via NHE inhibition has been suggested as a mechanism of these protective effects. The aim of this study was to examine whether treatment with amiloride analogues reduces the incidence of reperfusion arrhythmias and limits infarct size in vivo. Open-chest swine were exposed to a 30-minute left anterior descending artery (LAD) occlusion and 180 minutes of reperfusion during atrial pacing at 150 ppm. Intravenous 5-(N,N-dimethyI)-amiloride (AML, 5 μg/kg per min) was administered in the treatment group (n = 7) and intravenous saline in the control group (n = 7), starting 10 minutes before coronary occlusion. The infusion was continued during ischemia and reperfusion. The area at risk was defined by monastral blue dye and infarct size by triphenyltetrazolium chloride staining. Limb leads ECG and monophasic action potentials (MAPs) from the epicardium in the ischemic area were recorded. There was no significant difference in the size of the area at risk and hemodynamic parameters between the groups. However, the infarcted area was 0.4%± 1.0% of the area at risk in the treatment group, whereas it was 62%± 29% in the control group (P < 0.05). Pathological examination (Hematoxylin-eosin and mallory s phosphotungstic acid-hematoxylin staining) revealed that all of the infarcted area consisted of contraction band necrosis. MAP duration in both groups was significantly shortened during ischemia. After reperfusion, MAP duration in the treatment group recovered earlier than that of control group. However, there was no significant difference in the incidence of ventricular tachyarrhythmia between the groups. Inhibition of NHE with AML prevented reperfusion related cell necrosis in the in vivo swine model, but did not reduce the incidence of ventricular tachyarrhythmia.     

Sulphydryl group control of sodium-lithium countertransport kinetics: a membrane protein control abnormality in essential hypertension

Abstract. Erythrocyte sodium-lithium countertransport (SLC) is an obligatorily coupled equimolar exchange of intracellular sodium or lithium with extracellular sodium or lithium. SLC is partially inhibited by N-ethylmaleimide (NEM) but only when a transported ion (sodium or lithium) is present in the extracellular medium. In essential hypertensive patients with a strong family history of hypertension the Km of SLC for extracellular sodium was lower and Vmax tended to be higher than in normal controls, but the ratio Vmax/ Km gave a much clearer distinction between the two groups. After NEM treatment, the remaining SLC activity in normal individuals had a lower Vmax and Km for sodium but Vmax/Km was not affected. In essential hypertensives the remaining SLC activity after NEM again had lowered Vmax and Km but in these patients the Vmax/Km was much lower than in untreated erythrocytes and was then the same as in normal controls. On the assumption that NEM reacts with a -SH group on a membrane protein that regulates SLC, and that the ratio Vmax/Km reflects a rate constant for binding extracellular sodium to the unloaded carrier, the results suggest that (a) essential hypertensives have an increased rate of sodium binding to the transporter and (b) this is due to abnormal behaviour of a membrane -SH group.     

Tonic block of the Na+ current in single atrial and ventricular guineapig myocytes, by a new antiarrhythmic drug, Ro 22-9194

Summary— Ro 22-9194 reduced the Na⁺ current in the atrial myocytes as well as ventricular myocytes in a tonic block fashion. Ro 22-9194 had a higher affinity to the inactivated state Na⁺ channels (Kd₁ = 3.3 μM in atrial myocytes, Kd₁ = 10.3 μM in ventricular myocytes) than to those in the rested state (Kd_R = 91 μM in atrial myocytes, Kd_R = 180 μM in ventricular myocytes), which indicated that Ro 22-9194 had a higher affinity to the Na⁺ channels in atrial myocytes than in ventricular myocytes. Ro 22-9194 shifted the inactivation curve in the hyperpolarized direction in both atrial and ventricular myocytes. These findings suggest that Ro 22-9194 more strongly inhibited the Na⁺ channel of the atrial myocytes of the diseased hearts with the depolarized membranes potentials than the Na⁺ channels in ventricular myocytes.     

Levcromakalim decreases vascular tone, cytoplasmic Ca2+ and Ca2+ sensitivity in canine basilar artery

Summary— The involvement of large conductance Ca²⁺-activated K⁺ channels (BK) and ATP-sensitive K⁺ (K_ATP) channels in the regulation of canine basilar arterial tone was estimated in the presence of the agonist and blockers of these channels, by simultaneously measuring the changes in intracellular Ca²⁺ concentration ([Ca²⁺]_i) with the fura-2 microfluorimetric method. In the resting condition, levcromakalim reduced [Ca²⁺]_i and vascular tone. Levcromakalim suppressed the serotonin-induced increases in [Ca²⁺]_i and force of contraction, the maximum effects of which were much greater than those of nicardipine. The inhibitory effects of levcromakalim were blocked by glibenclamide but not by tetraethylammonium (TEA) or iberiotoxin (IbTX). In the presence of levcromakalim, the curve relating [Ca²⁺]_i with force in the presence of serotonin at different extracellular Ca²⁺ concentration ([Ca²⁺]_o) was shifted down- and right-ward compared with that in the absence of levcromakalim, suggesting that levcromakalim may reduce the Ca²⁺-sensitivity of the contractile proteins. Thus, levcromakalim may be a good candidate to suppress delayed cerebral vasospasm after subarachnoid hemorrhage.     

The urinary excretion of prostaglandins E2 and F2α in essential hypertension

The 24 h urinary excretions of prostaglandins E2 (E2/d) and F2 alpha (F2 alpha/d) were measured in twenty-five normal subjects and in thirty-five patients with essential hypertension [seventeen with low renin (LRH) and eighteen with normal renin (NRH) hypertension]. E2/d was lower in patients with LRH than in normal subjects (P less than 0.01), whereas no difference was found between patients with NRH and the controls. F2 alpha/d was similar in patients with LRH and in the normal subjects, but was significantly greater in patients with NRH (P less than 0.02). The ratio of prostaglandin E2 to prostaglandin F2 alpha was decreased in hypertensive patients (P less than 0.02), although in the NRH subgroup the difference was not statistically significant. It appears that LRH is associated with impaired production of prostaglandin E2, while a deranged relationship between the two prostaglandins exists in all the patients with essential hypertension. These changes in prostaglandin production could possibly contribute to the pathogenesis of hypertension, by increasing renal vascular resistance and decreasing sodium excretion. Alternatively, they might be a secondary phenomenon, reflecting changes in renal prostaglandin metabolism induced by the hypertensive state.     

中药补肾方对心力衰竭大鼠Na+-K+ATP酶、Ca2+-Mg2+ATP酶和琥珀酸脱氢酶的作用研究

目的研究补肾方对心力衰竭大鼠Na+-K+ATP酶、Ca2+-Mg2+ATP酶和琥珀酸脱氢酶(SDH)的作用。方法 60只大鼠随机分为模型组、假手术组、曲美他嗪组、补肾低、中、高剂量组,每组10只。采用结扎冠状动脉前降支法制备心力衰竭大鼠模型,术后2周开始灌胃,分别给予药物干预8周。8周后通过颈动脉插管记录大鼠血流动力学改变,包括左室收缩压(LVSP)、左室舒张压(LVEDP)、左室内压上升下降最大速率(±LVdp/dtmax);采用分光光度计检测心力衰竭大鼠心肌Na+-K+ATP酶、Ca2+-Mg2+ATP酶以及SDH水平。结果模型组大鼠心肌LVSP和+LVdp/dtmax较假手术组明显降低(P<0.01),而LVEDP和-LVdp/dtmax明显升高(P<0.05);补肾方干预后,中、高剂量大鼠心肌收缩、舒张功能明显优于模型组(P<0.01),以高剂量补肾方改善心力衰竭大鼠心功能明显。补肾方干预后,Na+-K+ATP酶、Ca2+-Mg2+ATP酶和SDH活力高于模型组,但低于假手术组,且随补肾方剂量增加,Na+-K+ATP酶、Ca2+-Mg2+ATP酶和SDH活力逐渐增强。结论补肾方可改善心力衰竭大鼠的心功能,可能与Na+-K+ATP酶、Ca2+-Mg2+ATP酶以及SDH活力增强相关。