Antihypertensive effects of acetic acid and vinegar on spontaneously hypertensive rats

To clarify the possibility of a preventive effect of dietary vinegar on blood pressure, long-term administration of vinegar or the acetic acid to SHR was examined. As a result, it was observed that acetic acid itself, the main component of vinegar, significantly reduced both blood pressure (p<0.05) and renin activity (p<0.01) compared to controls given no acetic acid or vinegar, as well as vinegar. There were no significant differences in angiotensin I-converting enzyme activity in various organs. As for the mechanism of this function, it was suggested that this reduction in blood pressure may be caused by the significant reduction in renin activity and the subsequent decrease in angiotensin II. From this study, it was also suggested that the antihypertensive effect of vinegar is mainly due to the acetic acid in it.     

Suprarenal aortic flow reduction versus angiotensin I infusion in fetal sheep

In the unanaesthetized fetal sheep, long-term suprarenal aortic blood flow reduction will cause upper body arterial blood pressure to increase. To see if the response to this procedure was entirely due to the concomitant increase in plasma renin activity, we gave an angiotensin I infusion of several days to 7 fetal sheep and compared their responses to those of 4 fetal sheep undergoing partial occlusion of the aorta above the renal arteries. Both protocols caused upper body arterial blood pressure to increase to comparable levels. Angiotensin I infusion had no effect upon venous blood pressure while suprarenal aortic blood flow reduction caused a significant increase in venous blood pressure as early as 1 day after blood flow reduction. Haematocrits were unchanged in the fetuses with flow restriction but increased in the infused fetuses. We conclude that long-term angiotensin I infusion in the fetus does not mimic the entire complex of responses to suprarenal aortic blood flow reduction.     

Evidence from a dual action of converting enzyme inhibitor on blood pressure in normal man

We studied the effect of a converting enzyme inhibitor (CEI), Captopril SQ 14,225 50 mg p.o. in eight supine normal subjects under a high sodium (150 meq/d) and low sodium (25 mEq/d) diet. On high sodium, plasma renin (PRA) and aldosterone were basal and Saralasin did not lower mean blood pressure. However, CEI induced an 11.4±3.2 mm fall in blood pressure (p<0.02) and either indomethacin 50 mg or ibuprofen 800 mg (PI), when given simultaneously on another day, abolished the blood pressure response (2.5±0.9 mm Hg, p>0.5). In contrast, on a low salt diet where renin was increased, CEI induced a drop in blood pressure which was not significantly altered by PI (12.8±1.1 vs. 10.0±3.1 mm Hg, p>0.5). CEI increased plasma renin on both diets (1.7±0.5 to 3.5±0.8 and 2.8±0.6 to 12.5±3.1 ng/ml/hr respectively both p<0.05). Aldosterone did not change (high Na⁺) or fell (low Na⁺). Inhibition of prostaglandin synthesis did not significantly block the renin rise from CEI suggesting that the direct angiotensin II negative feedback is relatively independent of acute prostaglandin release. Our studies suggest that CEI has a dual hypotensive action. In a low renin state, the hypotensive action appears to be mediated through vascular prostaglandins.     

Enalapril in the treatment of hypertension with renal artery stenosis.

The converting enzyme inhibitor enalapril, in single daily doses of 10-40 mg, was given to 20 hypertensive patients with renal artery stenosis. The blood pressure fall six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II and to the concurrent fall in angiotensin II. Blood pressure fell further with continued treatment; the long term fall was not significantly related to pretreatment plasma renin or angiotensin II concentrations. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, fallen further. The rise in active renin during long term treatment was proportionally greater than the rise in angiotensin I; this probably reflects the fall in renin substrate that occurs with converting enzyme inhibition. Enalapril alone caused reduction in exchangeable sodium, with distinct increases in serum potassium, creatinine, and urea. Enalapril was well tolerated and controlled hypertension effectively long term; only two of the 20 patients required concomitant diuretic treatment.     

树脂灌血液灌流在顽固性高血压患者血液透析中的应用

目的：探讨树脂灌血液灌流对血液透析顽固性高血压患者血压及肾素-血管紧张素．醛固酮系统的影响。方法：选择我院82例,均分为I组和II组各41例,I组患者采用金宝8LR聚酰胺膜透析器进行常规透析,II组患者在常规透析的基础上串联树脂血液灌流,检测两组患者治疗前和治疗后3个月血清肌酐、尿素氮变化情况,和患者体内肾素活性、血管紧张素II和醛固酮变化情况,并对血压变化值进行比较。结果：两组患者治疗后3个月血肌酐、血尿素氮均明显较治疗前降低,I组患者治疗后3个月收缩压和舒张压较治疗前均无明显变化,II组治疗后3个月收缩压和舒张压均较治疗前明显降低,I组治疗后3个月肾素、血管紧张素II和醛固酮较治疗前无明显差异,II组治疗后3个月肾素、血管紧张素II和醛固酮较治疗前均明显降低。结论：血液透析联合树脂吸附灌在保证有效清除患者体内代谢物质的同时角色较好的控制患者血压。     

Palmitoylethanolamide Treatment Reduces Blood Pressure in Spontaneously Hypertensive Rats: Involvement of Cytochrome P450-Derived Eicosanoids and Renin Angiotensin System

Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of angiotensin receptor 1 underlying pathways in mesenteric beds was shown in basal conditions in PEA-treated SHR. In conclusion, our data demonstrate the involvement of epoxyeicosatrienoic acids and renin angiotensin system in the blood pressure lowering effect of PEA.     

Effects of a nonperssor analogue of vasopressin on plasma renin activity and salt and water excretion in water-loaded,anesthetized dogs

The object of this study was to determine the importance of vasoconstrictor activity in the suppression of renin secretion by vasopressin. Arginine vasopressin (AVP) (0.05 and 0.1 ng/kg/min) and a nonpressor analogue of vasopressin, 1-deamino-[4-threonine, 8-D-arginine]-vasopressin (dTDAVP) (0.01 and 0.05 ng/kg/min), were infused intravenously in anesthetized hypophysectomized dogs. Neither dTDAVP nor AVP influenced arterial pressure or heart rate but both suppressed plasma renin activity. Infusion of dTDAVP at 0.01 and 0.05 ng/kg/min suppressed plasma renin activity to 86±4% (p<0.05) and 63±6% (p<0.01) of the control values respectively. Infusion of AVP at 0.05 and 0.1 ng/kg/min suppressed plasma renin activity to 60±8% (p<0.01) and 59±12% (p<0.05) of the central values respectively. dTDAVP and AVP both produced significant increases in sodium excretion. These data demonstrate that vasoconstrictor activity is not required for the effects of vasopressin on renin secretion and sodium excretion.     

Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets

Recent studies have demonstrated that the feeding of low protein diets to rats during pregnancy induces hypertension in their offspring. Maternal-diet-induced hypertension has been previously associated with elevated pulmonary angiotensin converting enzyme (ACE) activity. In the present study, the importance of the renin angiotensin system, and in particular ACE, in the maintenance of the hypertensive state, is investigated. Pulmonary and plasma ACE activity were determined in rats of different ages, following in utero exposure to 18 (control) or 9% (deficient) casein diets. No maternal diet induced changes in pulmonary ACE were noted, but at 4 and 13 weeks of age, plasma ACE activity was increased by 34 and 134%, respectively in 9% casein exposed rats relative to controls (P<0.001). Thirteen-week-old rats had significantly raised systolic blood pressure (28 mmHg, P<00.05), and tended to have higher diastolic blood pressure (not significant). These hypertensive animals had slightly raised plasma angiotensin II concentrations (30% higher, not significant), but similar renin activities, when compared with normotensive controls. Treatment of normotensive and hypertensive rats with the ACE inhibitor captopril demonstrated that higher plasma ACE activity may play a major role in the maintenance of maternal-diet-induced hypertension. Whilst normotensive rats showed no significant response to drug treatment, systolic blood pressure in the hypertensive rats fell rapidly to the level observed in the normotensive control group. Blood pressure remained at this lower level until treatment was withdrawn, at which time pressure began to increase slowly, but steadily. A period of 7–8 weeks was required following cessation of captopril administration for the restoration of hypertension.The data are consistent with the hypothesis that components of the renin-angiotensin system, and in particular plasma ACE, are involved in the maintenance of maternal-diet-induced hypertension.     

Effect of captopril (SQ 14225) on blood pressure,plasma renin activity and angiotensin I converting enzyme activity.

Seven patients with essential hypertension and seven patients with hypertension associated with renal artery stenosis received captopril (SQ 14225), an inhibitor of angiotensin I converting enzyme. There was a significant reduction in mean blood pressure, from 176/113 +/- 4/3 mm Hg during the control period to 140/90 +/- 5/3 mm Hg during captopril administration. Five patients received captopril alone and nine patients needed hydrochlorothiazide in addition to control their blood pressure. Captopril produced a significant increase in peripheral plasma renin activity. When measured 12 hours after the administration of captopril the angiotensin I converting enzyme activity was found to be similar to that during the control period even though the blood pressure was at or near normal. These findings indicate that although captopril is an effective antihypertensive agent, its action does not depend only on inhibition of plasma angiotensin I converting enzyme activity.     

Is sympathetic activation by stressful memories linked to the occurrence of hypertension and metabolic syndrome?

This paper is based on reported links between dementia and hypotension. Large clinical studies report that patients with Alzheimer's disease normalize previously elevated blood pressure. Among previously hypertensive, elderly persons, an unexpected minority of hypotensive elderly patients with cognitive decline has been found. A possible interpretation is that patients of both groups, instead of having cognition problems due to arterial hypotension, might have become hypotensive because they can no longer remember and worry about stress-inducing problems that have vanished from their memories.I propose that memory induced stress reactions increase the resting sympathetic tone, vascular resistance, secretion of renin and contrainsulary hormones. Dementia reduces this source of chronic stress reaction, and hence reduction on sympathetic activation could explain both the reduction in blood pressure and relief from insulin resistance. This might explain how is it possible that blocking of sympathetic activity and renin–angiotensin system prolongs human life, despite importance of these mechanisms in maintaining circulatory homeostasis in all mammals.     

Effect of prostacyclin infusion on active and inactive renin release in the isolated perfused kidney

The effect of prostacyclin infusion into the renal artery of the isolated perfused hog kidney on the release of active and inactive renin was investigated. Infusion of prostacyclin at a rate of 0.1 μg/min resulted in a significant increase (p<0.01) in active renin and a significant fall (p<0.01) in inactive renin. Prostacyclin also increased urinary kallikrein excretion (p<0.05). The results indicate that the kidney secretes not only active renin but also inactive renin, and suggest that prostacyclin stimulates the conversion of inactive renin to the active form through the activation of the renal kallikrein system.     

Effect of the protein-synthesis inhibitor actinomycin-D on the renin-angiotensin system in the rat.

The effect of actinomycin-D on blood pressure and the renin-angiotensin system has been studied in the rat. Treatment with the drug caused blood pressure, plasma renin activity and plasma renin substrate level to decrease. The results suggest that in the blood pressure-decreasing effect a reduction of the activity of the renin-angiotensin system had a role. This contradicts the view that actinomycin-D has no influence on renin production in the kidney.     

Inhibition of renin secretion in the isolated rat kidney by angiotensin I.

The effect of angiotensin I on renal perfusion pressure, and on basal and isoprenaline stimulated renin secretion, was examined in the isolated perfused rat kidney. The increase in prefusion pressure associated with intrarenal infusion of angiotensin I suggested conversion of the peptide to angiotensin II within the kidney. Basal renin secretion and the stimulatory response to isoprenaline were significantly suppressed by angiotensin I. The converting enzyme inhibitor SQ 20,881, infused at 1,600 X dose of angiotensin I, partially reversed the vasoconstrictor effect of angiotensin I without altering the degree of suppression of renin secretion.     

High strength vinegar fermentation by Acetobacter pasteurianus via enhancing alcohol respiratory chain

Seeking high strength vinegar fermentation by acetic acid bacteria (AAB) is still the mission of vinegar producers. AAB alcohol respiratory chain, located on intracellular membrane, is directly responsible for vinegar fermentation. In the semi-continuous vinegar fermentation by Acetobacter pasteurianus CICIM B7003, acetification rate showed positive correlation with the activity of the enzymes in alcohol respiratory chain. Aiming at achieving high strength fermentation process, a series of trials were designed to raise the activity of AAB alcohol respiratory chain. Finally, acetification was enhanced by adding some precursors (ferrous ions and β-hydroxybenzoic acid) of alcohol respiration associated factors and increasing aeration rate (0.14 vvm). As final result, average acetification rate has been raised to 2.29 ± 0.02 g/L/h, which was 28.7% higher than the original level. Simultaneously, it was found that the oxidization of alcohol into acetic acid in AAB cells was improved by well balancing of three factors: enzyme activity in alcohol respiratory chain, precursor of ubiquinone biosynthesis, and aeration rate.     

In vitro evaluation of physiological activity of vinegar produced from barley-, sweet potato-, and rice-shochu post-distillation slurry

Vinegar was produced from barley-, sweet potato-, and rice-shochu post-distillation slurry using jar fermentor within 19 hrs. All the vinegars showed radical-scavenging activity, angiotensin I converting enzyme (ACE) inhibition and advanced glycation endproducts (AGE) inhibition in vitro. The radical-scavenging activity of the vinegar produced from sweet potato-shochu post-distillation slurry was higher than that of other two kinds of vinegar on the organic matter basis. The ACE inhibitory activities of all the vinegars were higher than that of each post-distillation slurry. The main components that showed ACE inhibitory activity would be peptides, and their content increased during acetic acid fermentation. Regarding AGE inhibition, only rice-shochu post-distillation slurry did not show such activity, but the other two post-distillation slurries and all the vinegars showed clear inhibitory activity. The activity appeared to depend on the concentration of amino groups except for sweet potato-shochu post-distillation slurry and the vinegar produced from it.     

Blockade of renin or angiotensin for understanding human hypertension: a comparison of propranolol, saralasin and converting enzyme blockade.

To understand the role of the renin-angiotensin-aldosterone system in the pathogenesis of human hypertension, in serial studies we have blocked the system using three different pharmacologic probes: 1) reduction of renin secretion by administration of the beta receptor blocker, propranolol; 2) blockade of the action of angiotensin II by infusion of saralasin, a competitive antagonist of angiotensin II; and 3) blockade of the enzymatic conversion of angiotensin I to angiotensin II by infusing a nonapeptide competitive inhibitor. The depressor responses induced by either propranolol or the nonapeptide expose a significant to major involvement of excess renin--angiotensin in maintaining the hypertension of some 50 to 70% of common forms of hypertension including "essential" hypertension. This subgroup includes nearly all patients with high or "normal" renin--sodium profiles. The considerably lower estimates for a renin factor in essential hypertension suggested by saralasin testing now appear due to the partial agonism of this drug. Further studies are required to determine whether this relative or absolute excess of renin secretion is primarily involved in the hypertension and if not why it fails to shut itself off. Similar studies of normal subjects are also needed to determine whether renin support of blood pressure is proportionately greater or less than in hypertensive subjects. Meanwhile the validation provided by these three different pharmacologic probes portends a burgeoning clinical role for renin--sodium profiling not only in screening for renal and adrenal cortical hypertensions but also for characterizing the vasoconstrictor and volume elements involved in various individual patients and thus enabling more specific treatments of the various subtypes of essential hypertension.     

The renin-angiotensin system and the central nervous system.

One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons in the brain merits investigation.     

Effects of an angiotensin II antagonist; [sarcosine 1, isoleucine 8] angiotensin II, on blood pressure, plasma renin activity and plasma aldosterone concentration in hypertensive and normotensive subjects taking oral contraceptives.

To examine the involvement of renin-angiotensin-aldosterone system in the etiology of oral contraceptive induced hypertension, normal women (Group I), normotensive (Group II) and hypertensive (Group III) women taking Ovulen (R) were infused with a competitive angiotensin II (AII) antagonist, [1-sarcosine, 8-isoleucine] angiotensin II. The angiotensin II antagonist was infused at a rate of 600 ng/kg/min for 30 min 1.5 hrs after intravenous injection of 40 mg of furosemide. Blood pressure was monitored and pre-infusion and post-infusion plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined. Pre-infusion PRA and PAC showed no significant differences among these three groups. In response to the AII antagonist infusion blood pressure rose in Groups I and II, but blood pressure responses in Group III were variable. Four out of the total 6 subjects had pressor responses and only one subject had a significant blood pressure reduction. In both Groups I and II, PRA decreased and PAC rose after infusion of the antagonist. In Group III, PRA decreased to a lesser degree and PAC showed no consistent change. These data suggest that the renin-angiotensin-aldosterone system in hypertensive women or oral contraceptives is different from that of the normotensive users. However, the pathophysiology of oral contraceptive induced hypertension is not homogenous and angiotensinogenic hypertension is uncommon.     

Blood pressure reduction in hypertensive-diabetic rats by the somatostatin analog MK-678

A hypotensive effect of an orally-administered cyclopeptide somatostatin analog, MK-678, has been demonstrated in a hypertensive diabetic rat model. Sustained blood pressure reduction failed to occur when the drug was administered to the spontaneously hypertensive rat. The mechanism of hypotension appears independent of effects on a variety of hormones including insulin, glucagon, growth hormone, and components of the renin-angiotensin system including renin activity, plasma angiotensin converting enzyme, and aldosterone.     

用生料制备功能性双歧醋生产工艺的实验室研究

目的将双歧杆菌、醋酸菌、酵母菌和粉碎的制醋原料及麸曲共同发酵,通过生料制醋的方法来制备功能性双歧醋。方法将粉碎的玉米与麸曲、酵母液、麸皮和水搅拌均匀,使其经过液态糖化和酒精发酵后,接入醋酸菌和双歧杆菌(二者比例为1∶1),同时加入辅料,进行醋酸发酵,当检测到醋酸酸度为5.0%~7.5%时,加入食盐终止发酵,经过过滤,除菌澄清得到功能性双歧醋。结果双歧醋的最终醋酸度为3.2%,外观红棕色,光泽度好,清澈透明,无沉淀和悬浮物。总菌数:醋酸菌为3.3×1011/m l,双歧杆菌为1.9×107/m l;活菌数:醋酸菌为1.7×1011/m l,双歧杆菌为6.8×106/m l;大肠菌群数3个/100 m l;致病菌:不得检出。结论双歧杆菌及其代谢物可以在双歧醋中存活,生料固态发酵制备双歧醋的方法可行。