降血压乳酸菌发酵乳对原发性高血压大鼠的降压效果

目的对具有血管紧张素转化酶(ACE)抑制活性的乳酸菌DM9057发酵乳的抗胃肠道酶解能力及原发性高血压大鼠(SHR)体内降压效果进行研究。方法以10 ml/kg和2.5 ml/kg发酵乳一次性和连续灌胃原发性高血压大鼠。结果 DM9057发酵乳具有较好的抗胃肠道酶能力,并且2个剂量均具有较好的降血压效果,其中以10 ml/kg剂量效果最为显著,一次性和连续灌胃后,最大降压值为(17.97±3.82)、(25.46±5.06)mmHg。结论乳酸菌DM9057发酵乳具有较强的抗胃肠道能力,同时在原发性高血压大鼠体内能够发挥一定的降血压作用。     

Antihypertensive effects of onion on NO synthase inhibitor-induced hypertensive rats and spontaneously hypertensive rats

This study was designed to show the effects of onion on blood pressure in N(G)-nitro-L-arginine methyl ester (L-NAME) induced-hypertensive rats and stroke prone spontaneously hypertensive rats (SHRSP) using dried onion at 5% in their diets. For the experiment with L-NAME induced-hypertensive rats, male 6-weeks-old Sprague-Dawley rats were given tap water containing L-NAME to deliver 50 mg/kg BW/day. In this experiment, we found distinct antihypertensive effects of onion on the L-NAME induced-hypertensive rats and the SHRSP. Dietary onion decreased the thiobarbituric acid reactive substances (TBARS) in plasma in these hypertensive rats. Also, onion increased the nitrate/nitrite (products of nitric oxide (NO)) excreted in urine and the NO synthase (NOS) activity in the kidneys in SHRSP. These results suggested that the increased NO caused by the greater NOS activity, and additionally by the increased saving of NO by the antioxidative activity of onion, was one of the cause of the antihypertensive effect of onion in SHRSP. In the L-NAME induced hypertensive rats, onion did not significantly block the inhibition of NOS activity by L-NAME, and decreased nitrate/nitrite excretion in urine was not restored. The mechanism of the antihypertensive effect of onion probably involves increased saving of NO by antioxidative activity of onion in L-NAME induced-hypertensive rats.     

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.     

Potent hypotensive activity of 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine in spontaneously hypertensive rat

Chemically synthesized 1-O-hexadecyl-2-O-acetyl-$\text{sn}$-glycero-3-phosphocholine possessed the most potent hypotensive activity compared with bradykinin, prostagrandin E₂ and I₂ when 5 nano moles/kg body weight of each drug were administered intravenously in spontaneously hypertensive rat. The potency and the duration of hypotensive activity of 1-O-hexadecyl-2-O-acetyl-$\text{sn}$-glycero-3-phosphocholine were dose dependent. Exogenous norepinephrine or angiotensin II showed pressor activity during the hypotensive action of 1-O-hexadecyl-2-O-acetyl-$\text{sn}$-glycero-3-phosphocholine, but did not disturb the hypotensive pattern of this ether lipid. These may suggest that 1-O-alkyl-2-O-acetyl-$\text{sn}$-glycero-3-phosphocholine plays an important role for the regulation of blood pressure.     

1-O-hexadec-1'-enyl-2-acetyl-sn-glycero-3-phosphocholine and its biological activity

1-O-Alk-1'-enyl analog of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, alkylacetyl-GPC) was prepared semi-synthetically from choline plasmalogens of beef heart muscle. The main compound was identified mass spectrometrically as 1-hexadec-1'-enyl-2-acetyl-sn-glycero-3-phosphocholine (16:O alk-1'-enylacetyl-GPC, 16:O vinyl form of PAF) and its platelet aggregation activity was about one-fifth of that of the corresponding 16:O alkylacetyl-GPC. The irreversible platelet aggregation activity induced by 5X10(-10) M 16:O alk-1'-enylacetyl-GPC was completely inhibited by 5X10(-7) M CV-3988 and 1X10(-7) M L-652, 731, specific PAF antagonists, and more than 99% of the activity was also lost by acid treatment. The hydrogenated product, alkylacetyl analog, showed quite same activity as that of authentic 16:O alkylacetyl-GPC. The platelets desensitized with 16:O alkylacetyl-GPC and with 16:O alk-1'-enylacetyl-GPC were not aggregated with 5X10(-10) M 16:O alk-1'-enylacetyl-GPC, suggesting that alk-1'-enylacetyl-GPC occupied the same receptor site of alkylacetyl-GPC.     

Tissue catecholamine concentrations in spontaneously hypertensive rats

Tissue concentrations of noradrenaline (NA), dopamine (DA) and adrenaline (A) were compared in spontaneously hypertensive (SHR) and normotensive (NCR) rats, aged 1, 3, 8, 14 and 24 weeks The organs analyzed included the brain, subdivided into prosencephalon and rhombencephalon, heart, adrenal glands and kidney. Brain catecholamines were significantly lower in SHR than in NCR, and the difference appeared already at the age of 3 weeks. Concomitant increase was found in the adrenal NA and A concentrations of the SHR. Concentration of NA in the heart decreased in the SHR following onset of hypertension. It is concluded that the diminished NA, DA and A concentrations in the brain as well as the augmented adrenal NA and A levels in the SHR may be causally related to the development of hypertension, while the heart NA level reflects the secondary, hypertension -- related changes.     

Effects of acute exercise and prolonged exercise training on blood pressure, vasopressin and plasma renin activity in spontaneously hypertensive rats

The purpose of this study was to investigate the effect of swimming training on systolic blood pressure (BPs), plasma and brain vasopressin (AVP), and plasma renin activity (PRA) in spontaneously hypertensive rats (SHR) during rest and after exercise. Resting and postexercise heart rate, as well as blood parameters such as packed cell volume (PCV), haemoglobin concentration (Hb), plasma sodium and potassium concentrations ([Na+], [K+]) osmolality and proteins were also studied. Hypophyseal AVP had reduced significantly after exercise in the SHR, whereas PRA had increased significantly in the Wistar-Kyoto (WKY) strain used as normotensive controls. Plasma AVP concentration increased in both strains. By the end of the experiment, training had reduced body mass and BPs by only 10% and 6%, respectively. Maximal oxygen uptake was increased 10% and plasma osmolality 2% by training. The postexercise elevation of heart rate was not significantly attenuated by training. A statistically significant reduction in postexercise plasma osmolality (10%) and [Na+] (4%) was observed. These results suggested that swimming training reduced BPs. Plasma and brain AVP played a small role in the hypertensive process of SHR in basal conditions because changes in AVP contents did not correlate with those of BPs. Moreover, there were no differences between SHR and WKY in plasma, hypophyseal and hypothalamic AVP content in these basal conditions. Finally, during moderate exercise a haemodilution probably occurred with an increase of plasma protein content. This was confirmed by the exercise-induced increase of plasma AVP and the reduction of hypophyseal AVP content, suggesting a release of this hormone, which probably contributed to the water retention and haemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolism of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine in the human neutrophil

The biosynthesis of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-2-acetyl-GPC) together with that of 1-alkyl-2-acetyl-GPC (platelet-activating factor) has been demonstrated in a variety of inflammatory cells and tissues. It has been hypothesized that the relative proportion of these phospholipids produced upon cell activation may be influenced by their rates of catabolism. We studied the catabolism of 1-acyl-2-acetyl-GPC in resting and activated human neutrophils and compared it to that of 1-alkyl-2-acetyl-GPC. Neutrophils rapidly catabolize both 1-alkyl-2-acetyl-GPC and 1-acyl-2-acetyl-GPC; however, the rate of catabolism of 1-acyl-2-acetyl-GPC is approximately 2-fold higher than that of 1-alkyl-2-acetyl-GPC. In addition, most of 1-acyl-2-acetyl-GPC is catabolized through a pathway different from that of 1-alkyl-2-acetyl-GPC. The main step in the catabolism of 1-acyl-2-acetyl-GPC is the removal of the long chain at the sn-1 position; the long chain residue is subsequently incorporated either into triglycerides or into phosphatidylcholine. The 1-lyso-2-acetyl-GPC formed in this reaction is then further degraded to glycerophosphocholine, choline, or phosphocholine. 1-Acyl-2-acetyl-GPC is also catabolized, to a lesser extent, through deacetylation at the sn-2 position and reacylation with a long chain fatty acid. Stimulation of neutrophils by A23187 results in a higher rate of catabolism of 1-acyl-2-acetyl-GPC by increasing both the removal of the long chain at the sn-1 position and the deacetylation-reacylation at the sn-2 position. In a broken cell preparation, the cytosolic fraction of the neutrophil was shown to contain an enzyme activity which cleaved the sn-1 position of 1-acyl-2-acetyl-GPC and 1-acyl-2-lyso-GPC but not of 1,2-diacyl-GPC. Taken together, these data demonstrate that the human neutrophil is able to catabolize 1-acyl-2-acetyl-GPC in a manner both quantitatively and qualitatively different from that of platelet-activating factor. The differential catabolism may regulate the relative proportion of these two bioactive phospholipids in the neutrophil.     

Antihypertensive and cognitive effects of grape polyphenols in estrogen-depleted, female, spontaneously hypertensive rats

Both endogenous and dietary estrogens reduce hypertension and enhance cognitive abilities in estrogen-depleted female spontaneously hypertensive rats (SHR). Many of the beneficial effects of estrogens/phytoestrogens also appear to be provided by other polyphenols (e.g., proanthocyanidins) in grape seed, which lack appreciable estrogenic receptor binding. The present study tested the hypothesis that similar to phytoestrogens, proanthrocyanidins in grape seed polyphenols reduce salt-sensitive hypertension in young, estrogen-depleted SHR. SHR were ovariectomized at 4 wk of age and placed on phytoestrogen-free diets with or without 0.5% grape seed extract added and with high (8.0%) or basal (0.6%) NaCl. After 10 wk on the diets, grape proanthrocyanidin supplementation significantly reduced arterial pressure in the rats fed the basal (10 mmHg) and high (26 mmHg)-NaCl diet, compared with the nonsupplemented controls. In vitro superoxide production was significantly reduced (23%) by the grape seed polyphenols. Spatial learning (8-arm-radial maze) in the SHR on the basal NaCl diets was improved by dietary grape seed polyphenols. These results indicate that grape seed polyphenols decrease arterial pressure in SHR, probably via an antioxidant mechanism.     

Antihypertensive and vasorelaxant effects of water-soluble proanthocyanidins from persimmon leaf tea in spontaneously hypertensive rats

The antihypertensive and vasorelaxant effects of water-soluble proanthocyanidins, extracted in persimmon leaf tea, were investigated in spontaneously hypertensive rats, rat aortas, and human umbilical vein endothelial cells. Oral administration of proanthocyanidins significantly decreased the systolic blood pressure of the rats after 4 h, as compared with distilled water controls. A vasorelaxant effect on rat aortas was induced by proanthocyanidins, and it was abolished by removal of the endothelium and inhibition of endothelial nitric oxide synthase and soluble guanylyl cyclase activity. The phosphorylation levels of endothelial nitric oxide synthase (Ser-1177) and the upstream kinase Akt (Ser-473) in umbilical cells also increased in a time-dependent manner after the addition of a proanthocyanidin-rich fraction. These results suggest that the antihypertensive effect of proanthocyanidins in persimmon leaf tea is due to vasorelaxation via an endothelium-dependent nitric oxide/cGMP pathway, and that proanthocyanidins might be useful in dietary lowering of blood pressure.     

Antihypertensive effect of low ethanol intake in spontaneously hypertensive rats

Light to moderate drinking in humans lowers the risk of coronary heart disease and may lower blood pressure. We examined the effect of chronic low daily alcohol consumption on blood pressure, platelet cytosolic free calcium [Ca²⁺]_i, tissue aldehyde conjugates and renal vascular changes in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). We also examined the effects of the same weekly amount of alcohol consumption over a one day period each week simulating weekend drinking in humans. Animals, age 7 weeks, were divided into six groups of six animals each and were treated as follows: WKY and SHR control, normal drinking water; WKY and SHR, 0.5% ethanol in drinking water; WKY and SHR, 3.5% ethanol in drinking water one day/week. After 14 weeks systolic blood pressure, platelet [Ca²⁺]_i, liver, kidney and aortic aldehyde conjugates were significantly higher (p < 0.05) in untreated SHRs as compared to untreated WKYs. Daily 0.5% ethanol consumption in SHRs significantly (p < 0.05) attenuated these changes and also attenuated smooth muscle cell hyperplasia and narrowing of the lumen in small arteries and arterioles of the kidney. WKY rats treated with 0.5% ethanol had lower aldehyde conjugates without any significant effect on blood pressure and platelet [Ca²⁺]_i as compared to WKY controls. Consumption of 3.5% ethanol one day/week did not affect blood pressure and associated changes in normotensive WKY rats or hypertensive SHRs as compared to their respective controls. These results suggest that chronic daily low ethanol intake lowers blood pressure in SHRs by lowering tissue aldehyde conjugates and cytosolic free calcium.     

Antihypertensive and natriuretic effects of less-sodium soy sauce containing gamma-aminobutyric acid in spontaneously hypertensive rats

We investigated the mechanism of the antihypertensive effect of less-sodium soy sauce containing gamma-aminobutyric acid (GABA) in spontaneously hypertensive rats (SHRs). When SHRs were given a diet with less-sodium soy sauce containing GABA (GABA-rich soy sauce group) for 6 weeks, the systolic blood pressure decreased as compared with that in rats fed diets with less-sodium soy sauce or a solution of salt. Renal sympathetic nerve activity (RSNA) and positive Na balance were reduced, and the urinary Na excretion tended to increase in the GABA-rich soy sauce group. Vascular hypertrophy of the thoracic aorta and the coronary and renal interlobular arteries tended to reduce in the GABA-rich soy sauce group. These results suggest that inhibition of Na retention by natriuresis, as a result of inhibition of RSNA by the GABA in the soy sauce contributed to the antihypertensive effect of GABA in the SHRs. Intake of less-sodium soy sauce containing GABA might help to reduce overall cardiovascular risk.     

Antihypertensive effects of Undaria pinnatifida (wakame) peptide on blood pressure in spontaneously hypertensive rats

We examined the angiotensin I-converting enzyme (ACE) inhibitory activity and antihypertensive effect of the hot water extract of wakame, Undaria pinnatifida. Ten dipeptides were isolated from the extract by several steps of chromatography, and their amino acid sequences were Tyr-His, Lys-Trp, Lys-Tyr, Lys-Phe, Phe-Tyr, Val-Trp, Val-Phe, Ile-Tyr, Ile-Trp, and Val-Tyr. Both single administration and repeated oral administration of synthetic Tyr-His, Lys-Tyr, Phe-Tyr, and Ile-Tyr significantly decreased blood pressure in spontaneously hypertensive rats.     

Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus

Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.     

Vertebrate class distribution of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase in serum

Serum from numerous mammals and lower vertebrates contains an enzyme activity that is specific for the hydrolysis of the acetate moiety of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF, platelet activating factor). Acetylhydrolase (EC 3.1.1.47, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase) was found in all mammalian sera with activity ranging from 11 (fetal calf) to 178 (rabbit) pmol acetate liberated/microliter serum/min. The enzyme is not present in avian serum but is a constituent of reptiles and bony fishes.     

Action of 3-beta adrenolytics on plasma renin activity measured by radioimmunology in genetically hypertensive rats]

Spontaneously hypertensive rats (SHR) have basal levels of plasma renin activity (PRA) lower than the ones observed in normal Sprague Dawley rats. Three beta blocking agents are orally administered to unanesthetized spontaneously hypertensive and normotensive rats. Propranolol and S 464 reduce PRA in spontaneously hypertensive and normotensive control rats. Pindolol do not lower PRA in normotensive rats but increases levels of PRA in spontaneously hypertensive rats. These results are discussed.     

Antihypertensive treatment differentially affects vascular sphingolipid biology in spontaneously hypertensive rats

Background

We have previously shown that essential hypertension in humans and spontaneously hypertensive rats (SHR), is associated with increased levels of ceramide and marked alterations in sphingolipid biology. Pharmacological elevation of ceramide in isolated carotid arteries of SHR leads to vasoconstriction via a calcium-independent phospholipase A₂, cyclooxygenase-1 and thromboxane synthase-dependent release of thromboxane A₂. This phenomenon is almost absent in vessels from normotensive Wistar Kyoto (WKY) rats. Here we investigated whether lowering of blood pressure can reverse elevated ceramide levels and reduce ceramide-mediated contractions in SHR.

Methods and Findings

For this purpose SHR were treated for 4 weeks with the angiotensin II type 1 receptor antagonist losartan or the vasodilator hydralazine. Both drugs decreased blood pressure equally (SBP untreated SHR: 191±7 mmHg, losartan: 125±5 mmHg and hydralazine: 113±14 mmHg). The blood pressure lowering was associated with a 20–25% reduction in vascular ceramide levels and improved endothelial function of isolated carotid arteries in both groups. Interestingly, losartan, but not hydralazine treatment, markedly reduced sphingomyelinase-induced contractions. While both drugs lowered cyclooxygenase-1 expression, only losartan and not hydralazine, reduced the endothelial expression of calcium-independent phospholipase A₂. The latter finding may explain the effect of losartan treatment on sphingomyelinase-induced vascular contraction.

Conclusion

In summary, this study corroborates the importance of sphingolipid biology in blood pressure control and specifically shows that blood pressure lowering reduces vascular ceramide levels in SHR and that losartan treatment, but not blood pressure lowering per se, reduces ceramide-mediated arterial contractions.