THE EFFECTS OF CALCIUM ANTAGONISTS ON BLOOD PRESSURE AND RESPONSES TO α-ADRENOCEPTOR AGONISTS IN HYPERTENSIVE RABBITS

The effects of the calcium antagonists verapamil and nifedipine on mean arterial blood pressure, heart rate and pressor responses to a range of alpha-adrenoceptor agonists were examined in male normotensive New Zealand white rabbits and in rabbits with perinephritis hypertension. Verapamil and nifedipine caused a greater fall in mean arterial pressure in hypertensive compared to normotensive rabbits both when the fall was expressed as an absolute and as a percentage change. Effects on heart rate were similar in normotensive and hypertensive animals. Pressor responses to phenylephrine were attenuated by nifedipine and verapamil in normotensive and hypertensive rabbits. Pressor responses to alphamethyl noradrenaline were also attenuated by nifedipine, but pressor responses to BHT 920 were not significantly altered by either calcium antagonist in normotensive or hypertensive rabbits at the dose used. Thus the calcium antagonists had a greater effect on alpha 1 - than alpha 2-adrenoceptor mediated responses in both normotensive and hypertensive rabbits. Hypertensive animals showed an increased responsiveness to phenylephrine and alphamethyl noradrenaline but not BHT 920 compared to normotensives. This difference remained after treatment with both the calcium antagonists.     

THE BARORECEPTOR-HEART RATE REFLEX IN RENAL HYPERTENSION IN THE RABBIT

SUMMARY 1. The 'steady-state' properties of the baroreceptor-heart rate reflex were studied in twenty-one renal hypertensive and twenty-eight normotensive unanaesthetized rabbits. In each animal, intravascular pressures were varied by inflating balloons previously placed around the aorta and inferior vena cava. An average curve relating mean arterial pressure (MAP) to heart period (HP; pulse interval) was constructed for each group.
2. The average resting MAP was 134 mmHg (s. e. m. = 5.7) in hypertensive and 91 mmHg (s. e. m. = 4.0) in normotensive rabbits. The mean values for resting HP in the two groups were 254 ms (s. e. m. = 13.4) and 258 ms (s. e. m. = 3.2), respectively. The baroreflex-dependent heart period range (HPR) between the lower and upper plateau levels of the MAP-HP curve of hypertensive rabbits was about 80% of the normotensive value. The average gain (change in HP per unit change in MAP) in hypertensives was about 50% of the normotensive value. The threshold pressure for evoking an increase in HP during a rise in MAP, and the median blood pressure (i. e. MAP corresponding to half HPR), were both about 40 mmHg higher in the hypertensive group than in normotensive rabbits.
3. The parameter changes in the MAP-HP curve in renal hypertension are closely similar to those previously observed in patients with essential hypertension of the same severity. The baroreflex changes in essential hypertension are thus probably non-specific accompaniments of chronic blood pressure elevation.     

Effect of interleukin 8 and ICAM-1 on calcium-dependent outflow of K+ in erythrocytes from subjects with essential hypertension

INTRODUCTION: The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca2+ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca2+ dependent K+ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow. MATERIAL AND METHODS: The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43 +/- 3 years, mean body mass index (BMI) 27 +/- 0.5 and 22.3 +/- 0.3 kg/m(2), respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120 +/- 8 mmHg ). The other 37 (18 men, 19 women; mean age 39 +/- 3 years; BMI 23.8 +/- 0.5 kg/m(2) and 22.8 +/- 0.5 kg/m(2), respectively were normotensive healthy volunteers (mean arterial blood pressure 89 +/- 2 mmHg). All the patients and subjects were untreated for at least 4 weeks before blood sampling. RESULTS: Ca2+-dependent K+ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca2+-dependent K+ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence of TMB-8, a membrane calcium antagonist, significantly reduced the Ca2+-dependent K+ efflux. CONCLUSION: Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca2+ inflow in smooth muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca2+, thus inducing vasoconstriction in the smooth muscle cells.     

Effect of interleukin 8 and ICAM-1 on calcium-dependent outflow of K+ in erythrocytes from subjects with essential hypertension

SUMMARY

Introduction: The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca²⁺ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca²⁺ dependent K⁺ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow.

Material and methods: The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43?±?3 years, mean body mass index (BMI) 27?±?0.5 and 22.3?±?0.3?kg?m², respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120±8mmHg).The other 37 (18 men, 19 women; mean age 39?±?3 years; BMI 23.8?±?0.5?kg?m² and 22.8?±?0.5?kg?m², respectively were normotensive healthy volunteers (mean arterial blood pressure 89?±?2?mm?Hg).All the patients and subjects were untreated for at least 4 weeks before blood sampling.

Results: Ca²⁺-dependent K⁺ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca²⁺-dependent K⁺ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence

of TMB-8, a membrane calcium antagonist, significantly reduced the Ca²⁺-dependent K⁺ efflux.

Conclusion: Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca²⁺ inflow in smooth

muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca²⁺, thus inducing vasoconstriction in the smooth muscle cells.     

Studies on the autonomic nervous system in borderline hypertension

Summary Parameters of the autonomic nervous system were studied in normotensive subjects (NT; standing blood pressure (BP)125/85 mmHg) and in subjects with borderline hypertension (BHT; 140/90standing BP<60/100 mmHg). No differences in plasma noradrenaline and adrenaline levels were found between NT and BHT subjects, neither at rest nor during exercise at 75% of maximum work capacity. The dose of noradrenaline required to increase systolic BP by 10 mmHg was significantly higher in NT than in BHT subjects (5.13±0.42 vs 3.50±0.57 µg · min^–1). No difference between NT and BHT subjects was found in the dose of isoprenaline required to increase heart rate by 20 beats · min^–1 (1.21±0.12 vs 1.09±0.11 µg · min^–1). Resting salivary flow was significantly lower in BHT than in NT subjects (0.39±0.06 vs 0.98±0.06 g · min^–1), suggesting decreased parasympathetic activity in the former group. The enhanced pressor effect of noradrenaline, together with the decreased parasympathetic activity, could explain the elevated blood pressure and heart rate in subjects with borderline hypertension.     

Effects of gamma-vinyl GABA (vigabatrin) on blood pressure and body weight of hypertensive and normotensive rats

Summary Inactivation of GABA was inhibited by -vinyl GABA (GVG) and the effects of the increased GABA level in the brain on blood pressure and body weight of spontaneously hypertensive rats (SHR) and normotensive rats (WKY) were investigated.When started at the age of 8 weeks or 5 weeks, treatment of SHR and WKY with GVG (150 mg/kg, s.c.) for several weeks did not influence systolic blood pressure. In 1-week old SHR, treatment with GVG (up to 150 mg/kg, s.c.) abolished the rise in blood pressure until animals were 8 weeks old. Thereafter, arterial blood pressure started to increase but it remained distinctly lower than that in untreated animals. When started at the age of 1 week, treatment with GVG for 7 weeks did not influence arterial blood pressure in WKY. GVG delayed increase in body weight in SHR and WKY, irrespective of their age. GVG greatly increased GABA levels in the hypothalamus, frontal cortex, brainstem and rest of the brain in both WKY and SHR.It is concluded that an increase in the GABA level in the brain leads to a delay in the development of hypertension in young SHR. Hence, development of genetic hypertension seems to be susceptible to activation of the GABAergic system in a very early critical phase only. Send offprint requests to N. Singewald at the above addressThis work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung     

EFFECTS OF ONE-CLIP, ONE-KIDNEY HYPERTENSION IN CHRONICALLY CATHETERIZED PREGNANT EWES

1. Hypertension secondary to renal disease was studied in non-pregnant and pregnant ewes to determine whether there were any changes in arterial pressure and the distribution of cardiac output and, in particular, whether uteroplacental blood flow was affected. 2. In six non-pregnant, chronically catheterized, uninephrec-tomized ewes, a reduction in renal blood flow (RBF) to 40–50% of control caused hypertension within 3 h. This was maintained for as long as RBF was reduced (72 h) and returned to control 24 h after the occluder around the renal artery was released. When this experiment was repeated in 16 uninephrectomized pregnant ewes (118–134 days gestation) hypertension occurred within 3 h and was sustained for as long as RBF was reduced (between 24 and 72 h). Arterial pressure returned to control within 24–72 h of restoring RBF. 3. Compared with non-pregnant ewes, pregnant ewes had similar arterial pressures, higher cardiac outputs (CO; P < 0.001) and heart rates (HR; P < 0.001), lower total peripheral resistances (TPR; P < 0.001) and similar blood flows to brain, ovary, pancreas, kidney and spleen. Splenic vascular resistance (VR) was greater (P= 0.006), gut blood flow was greater (P < 0.05) and gut VR was less (P < 0.05). Myoendometrial blood flow/g was greater (P < 0.005) and myoendometrial VR was less (P= 0.006). 4. In pregnant sheep with renal clip hypertension, there was no change in CO and HR, but TPR increased (P < 0.01), as did plasma renin activity. Gut, brain, pancreatic and myoendometrial VR were increased as long as RBF was reduced; in addition, myoendometrial VR remained high for the rest of the experiment. Placental blood flow was unchanged at 3h; 24–72 h later it was reduced (P < 0.05) and remained low. Placental VR was increased 24–72 h after RBF was restored when ewes were again normotensive. 5. Thus, one-clip, one-kidney renal hypertension in the pregnant ewe was due to increased TPR associated with a fall in uteroplacental blood flow that persisted even when RBF was restored and ewes were normotensive. This reduction in uteroplacental blood flow could account for the high foetal morbidity and mortality that occurs in pregnant women with renovascular hypertension.     

NEUROPEPTIDE Y IN CORTISOL-INDUCED HYPERTENSION IN MALE VOLUNTEERS

1. Cortisol-induced blood pressure rises in men are not accompanied by increases in plasma catecholamines. The present study examines the effects of cortisol on the sympathetic co-transmitter, neuropeptide Y (NPY). 2. Eight normal men were given cortisol 200 mg/day over 5 days and haemodynamic, metabolic and hormonal measures were taken. Plasma NPY-like immunoreactivity (NPY-LI) concentrations were measured by direct radio-immunoassay. 3. Cortisol significantly increased systolic, diastolic and mean arterial pressure, bodyweight, plasma glucose and total white cell concentration and decreased plasma potassium and total eosinophil count, as in previous studies. Plasma NPY concentrations were not altered significantly during cortisol treatment, but increased following cessation of cortisol treatment (P= 0.006). 4. The essentially unchanged pattern for NPY concentration with cortisol treatment resembles that previously reported for adrenaline and noradrenaline, but the increase in NPY on cortisol withdrawal was not seen for adrenaline or noradrenaline. These data do not support a role for sympathetic activation in the genesis of cortisol-induced hypertension.     

ROLE OF PLATELET CYTOSOLIC CALCIUM IN THE RESPONSE TO SALT INTAKE IN NORMOTENSIVE SUBJECTS

1. To investigate the role of cytosolic calcium in salt-induced hypertension, a high salt diet was given to young normotensive subjects with or without a family history of hypertension. 2. A high salt diet raised blood pressure significantly in normotensive subjects with a family history compared with the age and gender matched subjects without a predisposition to hypertension. 3. Platelet cytosolic calcium was increased in predisposed subjects in a control period before salt intake. 4. A positive correlation was observed between the changes in mean blood pressure and cytosolic calcium before high salt intake, although salt loading did not induce any significant change in cytosolic calcium. 5. These results suggest that cytosolic calcium plays a role in elevation of blood pressure induced by salt loading in subjects with a family history of hypertension.     

EFFECTS OF NEONATAL SYMPATHECTOMY BY 6-HYDROXYDOPAMINE ON BLOOD PRESSURE AND INTRAVASCULAR VOLUME IN YOUNG STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1. Stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) were 'chemically sympathectomized' immediately after birth with 6-hydroxydopamine (6-OHDA, 100 mg/kg s.c. daily) for the first 10 days of life. 2. Body weight gain was diminished in both groups as compared with sham-treated controls. Blood pressure was reduced in 'sympathectomized' SHRSP, and also WKY rats had a slightly lower blood pressure than control rats. 3. Plasma concentration of angiotensin II and renin content of the kidney were not influenced by 6-OHDA. 4. 'Sympathectomized' SHRSP retained similar amounts of sodium than sham-treated SHRSP when sodium retention is expressed per body weight gained. Plasma and blood volumes were increased in both SHRSP and WKY rats, whereas packed cell volume was significantly decreased. 5. These results demonstrate the significance of an intact sympathetic nervous system for the development of hypertension in SHRSP. The expanded plasma and blood volume in 'sympathectomized' rats indicate an important role of the sympathetic nervous system and/or the arterial blood pressure for the regulation of intravascular volume.     

A RANDOMIZED CONTROLLED TRIAL OF THE EFFECT OF ALCOHOL CONSUMPTION ON BLOOD PRESSURE

Forty-six healthy normotensive male drinkers participated in a randomized, controlled, crossover trial to study the effects of varying alcohol intake on blood pressure. Alcohol consumption (calculated from weekly diaries) was reduced from 336.3 (s.e.m. = 20.2) to 64.5 (s.e.m. = 5.6) ml ethanol/week by drinking low alcohol content beer alone. Systolic blood pressure fell significantly during reduction of alcohol intake and rose again when normal drinking habits were resumed, the mean difference during the last 2 weeks of normal or low alcohol intake being 3.8 mmHg. This effect of alcohol on blood pressure was independent of a small but significant decrease in weight following reduction of alcohol intake. The change in blood pressure correlated with change in alcohol consumption (r = 0.53, P less than 0.001) with a 1 mmHg fall predicted for each 100 ml of reduction in ethanol intake/week. We conclude that regular moderate alcohol consumption has a direct (but reversible) pressor effect in normotensive men.     

The effects of intracerebroventricular injection of clonidine on conditioned pressor and adrenergic responses in rats

Studies from this laboratory have shown that the first filial offspring of female spontaneously-hypertensive rats and male Wistar-Kyoto (WKY) normotensive rats develop stress-induced hypertension. The present study sought to examine the effects of intracerebroventricular administration of clonidine (8 micrograms) on cardiovascular and sympathoadrenal responses to aversive classical conditioning in these borderline hypertensive rats (BHR) and in normotensive WKY control rats. Clonidine caused significant reductions in resting arterial pressure, vascular resistance, heart rate and concentrations of epinephrine (E) in plasma for both hypertensive and normotensive rats. Central administration of normal saline to control rats of each strain did not alter basal cardiovascular or sympathoadrenal function. The presentation of a conditioned stimulus (CS) elicited a significant increase in arterial pressure and total peripheral resistance in hypertensive rats treated with saline and clonidine and in normotensive rats treated with saline. In contrast, normotensive rats treated with clonidine showed no increases in arterial pressure or vascular resistance following the onset of the conditioned stimulus. The aversive conditioning session instigated significant increases in the concentrations of norepinephrine (NE) and E in plasma in saline-treated rats. Hypertensive and normotensive rats treated with clonidine-showed a blunted increase in plasma concentrations of NE and E during this period; however, concentrations of E in hypertensive rats increased significantly from the baseline period after injection. These data suggest that an abnormality in central alpha 2-adrenoceptor-mediated inhibition of sympathoadrenal discharge and sympathetic vasomotor tone may predispose the hypertensive rat to develop stress-induced hypertension.     

SLOW PRESSOR EFFECT OF ANGIOTENSIN II IN NORMOTENSIVE RATS WITH RENAL ARTERY STENOSIS

1. We have shown previously that renal artery stenosis in rats causes enhanced responsiveness to the slow pressor effect of angiotensin II (AngII) and suggested that two-kidney, one clip (2K1C) hypertension may depend, in part, on changes in responsiveness to the peptide. 2. The present experiment was performed in order to investigate whether a degree of renal artery stenosis that was insufficient to raise blood pressure was able to enhance responsiveness to the slow pressor effect of AngII. 3. Two to four weeks after placement of a 0.2 mm clip over the left renal artery (2K1C) or a sham operation, some 2K1C rats were normotensive. These rats and the sham rats then received an intravenous infusion of AngII (4 ng/min) for 10 days. 4. AngII caused the 2K1C rats to attain significantly higher mean arterial pressure than the sham rats (152 ± 7 vs 133 ± 7 mmHg) and did not result in water or electrolyte retention in the 2K1C rats. 5. These results indicate that normotensive 2K1C rats exhibit enhanced responsiveness to the slow pressor effect of AngII and that the arterial pressure response to renal ischaemia may depend on both AngII formation and responsiveness to the chronic actions of the peptide.     

The haemodynamic response to propranolol in cirrhosis with arterial hypertension: a comparative analysis with normotensive cirrhotic patients

Aliment Pharmacol Ther 2010; 32: 105–112

Summary

Background Cirrhosis with arterial hypertension is not uncommon. Haemodynamic alterations in these patients and the effects of beta‐blocker on hepatic venous pressure gradient (HVPG) and systemic haemodynamics have not been evaluated. Aims To compare the systemic haemodynamic alterations in hypertensive and normotensive cirrhotics, and to investigate the effects of propranolol on these parameters. Methods A retrospective analysis of consecutive hypertensive cirrhotic patients (n = 33) who underwent haemodynamic assessment and paired HVPG measurement was done. Normotensive cirrhotics (n = 50) served as controls. Results Hypertensive patients had a significantly higher heart rate, systemic (SVRI), and pulmonary vascular resistance. There was a significant reduction in mean arterial pressure (MAP) in the hypertensive cirrhotic group from 112 (107–130) mmHg to 95 (77–114) mmHg (P < 0.01), but no change in the normotensives. SVRI remained the same in the hypertensive cirrhotic group, but it increased in the normotensives. There was no correlation between MAP reduction and HVPG reduction. Conclusions The frequency of HVPG response with propranolol treatment in hypertensive cirrhotics is similar to normotensive cirrhotics. Propranolol treatment reduces MAP significantly in hypertensive patients with cirrhosis. Treatment with a nonselective beta‐blocker is a good strategy for hypertensive cirrhotic patients.     

Prostaglandin synthesis inhibition with indomethacin in ACTH-induced hypertension

The short- and long-term effects of indomethacin administration were examined in normotensive and ACTH-induced hypertensive conscious sheep. Indomethacin, 1 mg/kg/h for 60 min, caused a transient rise in mean arterial pressure (MAP) and calculated total peripheral resistance (CTPR) and a fall in cardiac output in normotensive sheep. In sheep with ACTH hypertension, these haemodynamic effects were prolonged. Indomethacin infusion at 3 mg/kg/day for 3 days had no observable haemodynamic or metabolic effects. Concomitant infusion of ACTH increased MAP and CTPR. These studies suggest prostaglandins play only a minor role in regulation of blood pressure in normal conscious sheep, but modulate the blood pressure rise in ACTH hypertension in sheep.     

ALCOHOL AND BLOOD PRESSURE IN A WORKING POPULATION

1. The association between alcohol consumption and blood pressure was studied in 491 Government employees. The men, aged 21–45 years, volunteered to complete a health questionnaire and submitted to standardized measurements of blood pressure, heart rate and body size. 2. Average weekly alcohol consumption correlated with systolic pressure (R = 0.18, P<0.001) but not with diastolic pressure. Systolic pressure increased progressively with increasing alcohol consumption with no obvious threshold effect. An effect of alcohol was seen independent of age, obesity (Quetelet's index) or cigarette smoking. 3. Results indicate that alcohol ranks close to obesity as a preventable cause of essential hypertension in the community.     

RENIN AND ANGIOTENSIN-CONVERTING ENZYME GENOTYPES IN PATIENTS WITH ESSENTIAL HYPERTENSION AND LEFT VENTRICULAR HYPERTROPHY

1. The associations between left ventricular hypertrophy (LVH) and specific alleles of the renin and angiotensin-converting enzyme (ACE) genes were studied in patients with essential hypertension and normal blood pressure. 2. LVH was present in 42% of those with essential hypertension (n= 72) and 17% of those with normal blood pressure (n= 44). 3. The frequency of each renin allele was the same in hypertensive and in normotensive patients. Renin allele frequencies were also the same for those with LVH and those with normal cardiac mass. When only hypertensives were considered, renin alleles were in the same proportion for the groups with and without LVH. Similarly, ACE alleles were not associated with essential hypertension nor with elevated cardiac mass. 4. We conclude that, in this population, variations in the renin or ACE genes do not contribute significantly to the development of LVH or to essential hypertension.     

Brachial artery cross-sectional area and distensibility before and after arteriolar vasodilatation in men with sustained essential hypertension

Blood pressure, volume distensibility (VD), and cross-sectional area (CSA) of the brachial artery were studied using pulsed Doppler systems in 51 patients with sustained essential hypertension in comparison with 21 normotensive controls of the same age. In hypertensive patients, in baseline conditions, CSA was significantly increased and VD decreased--the two parameters strongly and negatively correlated independent of the blood pressure level. Arteriolar vasodilatation was produced by three pharmacological agents--cadralazine, a dihydralazine-like compound; nicorandil, a nicotinamide derivative; and nitrendipine, a calcium entry blocker. For the same blood pressure reduction, cadralazine significantly reduced CSA, while nicorandil and nitrendipine increased it. Nitrendipine significantly increased VD, which was not modified by cadralazine and nicorandil. For cadralazine and nicorandil, a significant negative correlation was observed between VD and CSA. The relationship was the same as in baseline conditions. With nitrendipine, no significant correlation was observed between the two parameters. At any given CSA, distensibility was higher with nitrendipine than with cadralazine or nicorandil. The study provided evidence that, in men with essential hypertension, in basal conditions, the negative relationship between VD and CSA reflected intrinsic alterations of the arterial wall, while cadralazine, nicorandil, and nitrendipine caused a similar degree of arteriolar dilatation, nicorandil and nitrendipine caused active arterial dilatation as well, and changes in distensibility after drug administration were not directly related to blood pressure level and were mediated either by predominant geometrical modifications (cadralazine, nicorandil) or by the predominant relaxing effect of the drug on arterial smooth muscle tone (nitrendipine), or both.     

口服螺内酯对SHR心肌组织TNF-α表达的影响

目的:观察口服小剂量螺内酯对自发性高血压大鼠(SHR)心肌组织TNF-α表达水平的影响.方法:20只8周龄雄性SHR随机分为螺内酯组和安慰剂组,每组10只,另设对照组(Wistar-kyoto,n=7).螺内酯组螺内酯双蒸水溶解,20 mg/(kg·d)灌胃,安慰剂组和对照组等容积双蒸水灌胃,持续16周,24周龄大鼠称取体质量,颈动脉插管检测动脉血压.摘取心脏,心尖部横断为两片,分别投入液氮罐中和10％中性甲醛固定液中,用ELASA方法检测心肌组织匀浆上清液TNF-α水平,免疫组化观察TNF-α表达.结果:螺内酯组与安慰剂组比较,收缩压、舒张压、平均动脉压水平无明显变化(P＞0.05),但两组的收缩压、舒张压、平均动脉压均明显高于对照组,差异有统计学意义(P＜0.05).安慰剂组与对照组比较,心肌组织TNF-α水平明显升高,螺内酯组与安慰剂组比较心肌组织TNF-α水平降低,差异有统计学意义(P＜0.01),但未达对照组水平(P＞0.05).结论:SHR大鼠心肌组织TNF-α高表达,口服小剂量螺内酯可降低SHR大鼠心肌组织TNF-α水平.     

Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension

Relationship between occupational exposure to lead and frequency of complications in persons with arterial hypertension has been poorly investigated. This study aimed at evaluation of the relationship between occupational exposure to lead and manifestation of an increased local arterial stiffness and left ventricular diastolic dysfunction. The studies included 105 men (mean age: 44.47 ± 9.12 years) with arterial hypertension, treated with hypotensive drugs: group I — men occupationally exposed to lead (n = 53), and group II — men not exposed to lead (n = 52). In echocardiographic examination, the left ventricular diastolic dysfunction was diagnosed significantly more frequently in group I than in group II. In eTracking examination mean values of stiffness parameter (β), augmentation index (AI) and one-point pulse wave velocity (PWV-β) were significantly higher and mean values of arterial compliance (AC) were significantly lower in group I than in group II. The logistic regression showed that in the group of persons with arterial hypertension occupationally exposed to lead a more advanced age, higher blood lead concentration and higher mean values of augmentation index represent independent risk factors of left ventricular diastolic dysfunction. The multifactorial regression showed that amongst persons with arterial hypertension occupationally exposed to lead higher blood zinc protoporphyrin concentration, a more advanced age and higher value of body mass index (BMI) represent independent risk factors of an increased local arterial stiffness. In summary, we should note that in the group of persons with arterial hypertension occupationally exposed to lead the study has demonstrated a significantly more frequent manifestation of left ventricular diastolic dysfunction and an increase in local arterial stiffness.