Some alterations of lipid metabolism in spontaneously hypertensive rats in relation to the stage of hypertension.
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Biomedical subjects
Publications and source records attributed to V Moritz.
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Fifty-two outpatients requiring domiciliary nebulised bronchodilator therapy were studied to determine the frequency and degree of contamination of nebuliser solutions and equipment. In 32 of the 52 patients (61%) nebuliser solutions and/or aerosols were contaminated. The degree of contamination was greater than that of ambient air in 90% of the contaminated aerosols. Diluent solutions were more frequently contaminated than salbutamol solutions (51% vs. 9%) and the organisms isolated from the solutions frequently correlated with those in aerosols. Gram-negative bacilli, particularly Pseudomonas species, were the most frequently isolated organisms.
The effect of diets rich or deficient in polyunsaturated fatty acids (PUFA) on blood pressure of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (WR) was studied. The diets contained either sunflower oil (PUR-SOL), linseed oil (PUR-LIN), cod-liver oil or hydrogenated palm-kernel oil (PUFA-deficient) amounting to 15 or 3 weight percent of fat. They were started at weaning (4 weeks of age) for 22 weeks or prenatally one week before mating of the parents. During the development of hypertension in SHR, systolic blood pressure was decreased in animals of all dietary groups fed 15% fat when compared to SHR on normal food (pellets), i.e. independent of the various diets loaded, all diets containing 15% fat led to a marked delay in the onset of high blood pressure as compared to SHR on normal pellet food. After manifestation of hypertension, obviously a more differentiated effect on blood pressure could be shown in SHR in dependence on different amounts of PUFA loaded. In normotensive Wistar rats (WR) after feeding linseed oil or sunflower oil also a significant lowering in blood pressure could be observed in comparison to controls fed pellets. But after feeding cod-liver oil there was no decrease in blood pressure of normotensive Wistar rats, whereas palm-kernel oil resulted in a blood pressure lowering effect only at the later age of normotensive Wistar rats. Moreover, in SHR after prenatal feeding of a LA-rich, but also a PUFA-deficient diet the blood pressure lowering effect was more pronounced as compared to postnatal feeding of the diets. SHR fed a 15% fat diet showed a significantly lower body weight in comparison to SHR fed a 3% fat diet. In both dietary groups SHR were significantly smaller than SHR fed pellets. In WKY fed a 3% or a 15% fat diet the same body weight could be confirmed. Food intake in SHR fed a 3% fat diet ad libitum appeared higher than in SHR fed a 15% fat diet ad libitum. However, considering the uptake of energy no differences between the groups could be seen. Therefore, in SHR fed a 15% fat diet, body weight and blood pressure were lowest when compared with the other groups of SHR indicating that body weight in SHR might be nearly connected with blood pressure level.(ABSTRACT TRUNCATED AT 400 WORDS)
The lipid content as well as the fatty acid pattern of triglycerides, free fatty acids (FFA), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were estimated in renal cortex and medulla of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (WR) at 4, 8, 26 and 52 weeks of age. In general, the level of triglycerides in renal medulla appeared higher when compared with the cortex. On the other hand, PC and PE, increasing with age, were usually higher in the cortex. A decreased percentage of linoleic acid (LA) in triglycerides, of arachidonic acid (AA) in PC and of eicosapentaenoic acid (EPA) in triglycerides, FFA, PC and PE could be found in the kidneys of SHR at 8 weeks of age, i.e. during the development of hypertension. This was accompanied with a rise of AA in FFA of SHR at 8 weeks of age, which occurred with delay in WR (at 26 weeks of age). From the data presented it can be concluded that systematic alterations in the availability of individual polyunsaturated fatty acids (PUFA) in various renal lipids might be related to the onset of hypertension in SHR which should be elucidated in more detail.
In spontaneously hypertensive rats (SHR) fed a linoleic acid-rich (LAR) diet over 22 weeks blood pressure could not be influenced when compared with SHR on linoleic acid-deficient (LAD) food. On the other hand, normotensive Wistar rats (WR) revealed a significantly lower blood pressure after feeding a LAR diet. The percentages of LA and AA were markedly increased in triglycerides and free fatty acids (FFA) in renal cortex and medulla of LAR-fed SHR and WR in comparison to LAD-fed animals. In renal phosphatidylethanolamine (PE) LA was also increased whereas AA remained unchanged. On the contrary, in phosphatidylcholine (PC) LA was only slightly augmented (in SHR) or even lowered (in WR), AA appearing decreased in SHR but increased in WR. These different changes in PE and PC indicate that individual phospholipids show a dissimilar behavior after dietary interventions, which can be masked by the evaluation of total phospholipids and might be of pathophysiological relevance.
Linoleic acid-rich (LAR), linolenic acid-rich (LNAR) and linoleic acid-deficient (LAD) diets in spontaneously hypertensive rats (SHR) and normotensive rats (NR) resulted in various changes in n-6 and n-3 fatty acids of lipids in renal medulla. After LAR diets the percentage of linoleic (LA) and arachidonic acids (AA) was high only in triglycerides (TG) and free fatty acids (FFA). In phosphatidylethanolamine (PE) LA was increased after LAR diet, whereas AA remained unchanged. In phosphatidylcholine (PC) LA was higher, but AA appeared lower as compared to LAD fed SHR. After LNAR diet linolenic (LNA) and eicosapentaenoic acids (EPA) were increased, but AA appeared significantly lower. Consequently, the lowest percentage of AA was found after LNAR diet. Blood pressure could not be influenced by the diets.
104 spontaneously hypertensive rats (SHR) and 107 normotensive control rats (WR) fed a commercial diet were sacrificed at 4, 8, 26 and 52 weeks of age. The kidneys were immediately removed and carefully separated into cortex and medulla. In general, the triglyceride levels in renal medulla appeared higher when compared with the cortex. On the other hand, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were usually higher in the cortex and increased with age. In the kidneys of SHR at 8 weeks of age, i.e. during the development of hypertension, the percentage of linoleic acid (LA) in triglycerides and of arachidonic acid (AA) in PC was decreased. This was associated with an increase of AA in free fatty acids (FFA), indicating an enhanced activity of phospholipase A2. Furthermore, a fall of eicosapentaenoic acid (EPA) in triglycerides, FFA, PC and PE of kidneys in SHR at 8 weeks of age could be found. The data suggest that systematic alterations in the availability of individual polyunsaturated fatty acids in various renal lipids might be related to the onset of hypertension in SHR. Age-dependent changes in enzymes involved in prostaglandin formation should be considered as an adaptive mechanism which is insufficient to reduce or abolish genetically determined hypertension in SHR.
Serum triglycerides appeared significantly lower in spontaneously hypertensive as compared to normotensive rats except in 8-week-old animals. Tri-, di and monoglycerides decreased continuously with age in the former but revealed only a transient fall in the latter. The remarkably high portion of partial glycerides (about 30% of total glycerides) in serum should be considered in all studies on lipolysis in rats.
The fatty acid pattern of serum triglycerides and cholesterol esters has been estimated in spontaneously hypertensive rats (SHR) and normotensive Wistar rats (WR) at 4, 5, 6, 7, and 8 weeks of age. The percentage of linoleic acid (LA) was lower in SHR when compared with WR, but increased with age in both strains. Arachidonic acid (AA) showed an abrupt fall in SHR and WR at 5 weeks of age in comparison to 4 week old rats. The fall was more pronounced in serum triglycerides of the former and in cholesterol esters of the latter. The changes in AA occurred prior to the onset of hypertension in SHR. From the data it can be concluded that the formation of AA from LA might be dependent on age being quantitatively different in SHR and WR. Furthermore, eicosapentaenoic acid (EPA) appeared lower in SHR than in age-related WR. Docosapentaenoic and docosahexaenoic acids also revealed a marked decrease in rats between 4 and 5 weeks of age indicating that individual polyunsaturated fatty acids (PUFA) change in a different manner which might be relevant to the development of high blood pressure in SHR.
Of 200 patients, 6.5% were skin carriers of Staphylococcus aureus and 3.5% became skin carriers after admission. Development of skin carrier state was associated with a long preoperative hospital stay. A second study of 275 cases showed that skin carriers of S. aureus had a significantly higher subsequent staph wound infection rate than non-carriers, but nose and/or throat carriers of S. aureus did not. Peroperative wound contamination was a significant factor in the subsequent development of wound infection. In clean surgery the infection rate was 5.9%. Both wound contamination and infection was due to gram positive organisms, usually S. aureus. When the gastrointestinal or biliary tract had been opened, the infection rate was 28%, the usual contaminating and infecting organisms were enteric and only occasionally S. aureus. There is a need for improved methods of minimizing peroperative wound contamination.
The morphological reactions and the long-term vasotonus behaviour of the coronary microvasculature including its smallest ramifications as well as the relationships existing between these reactions and the myocardial activity in the different stages of spontaneous hypertension of rats (SHR) are unknown. Therefore 80 1-12 month-old male SH- and 60 normotensive Wistar control rats were histomorphometrically investigated. Already in the prestage of hypertension (1 month) an increase of wall thickness and phosphatase activity in blood vessels alpha less than 10,5 microns occurred. These appearances of vasotonus increase were regressed in the acute phase (2nd-4th month). When the rise of myocardial activity is lowered in the stabile stage the mentioned signs of vasotonus increase returned (6th month) and showed a strong spreading in the late stage (12th month), which is characterized by enzyme histochemically detected disturbances of heart muscle metabolism. The behaviour of long-term vasotonus of the microvasculature and myocardial metabolism in 6 month-old and older rats provides a hypothesis concerning the cause of the unknown increase of coronary contraction in the stabile phase. It points to the existence of a vicious circle which perhaps plays a role in the genesis of heart insufficiency in hypertension.
Spontaneously hypertensive rats (SHR) and normotensive Wistar rats were fed a linoleic acid-rich (LAR) and -deficient (LAD) diet for 22 weeks, respectively. Although linoleic acid (LA) and arachidonic acid (AA) in serum and liver triglycerides markedly increased after a LAR diet, LA was significantly lower and AA was higher in SHR when compared to normotensive control rats. Thus, the percentage of both fatty acids remained different like in animals fed a commercial diet. On the contrary, in SHR and normotensive rats fed a LAD diet no differences in the LA and AA content could be found between the groups. In these rats, however, n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) in serum triglycerides were increased. Blood pressure, serum triglycerides and total cholesterol appeared unchanged, whereas HDL-cholesterol was increased after a LAR diet. Dopamine, adrenaline and noradrenaline content as well as dopamine-beta-hydroxylase activity were augmented in adrenal glands of SHR fed a LAR diet. In spite of distinct biochemical alterations the genetically determined hypertension in rats could not be influenced by a long-lasting diet containing a high amount of LA which has been proved to be effective on lowering blood pressure in other hypertensive rat models.
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Incorporation of 32P into di- and triphosphoinositides of erythrocytes from 1-month-old spontaneously hypertensive rats was lower, and diphosphoinositide content higher, than in controls. During development of hypertension these initial differences decreased and were even reversed.
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Substance P (SP) and an analogue (Lys-Phe-Ile-Gly-Leu-MetNH2 = EH) were tested in acute experiments on the blood pressure in the intact rat anaesthetized with urethane. A biphasic response, consisting of an initial depressor, followed by a pressor component, was seen. In low concentrations, SP decreases blood pressure, in medium concentrations SP produces a pronounced biphasic response, in high concentrations SP produces only hypertensive reactions. In chronic experiments, SP-peptides act also in different directions. After EH, disorders in avoidance learning were completely eliminated from 10 weeks old spontaneously hypertensive rats (SHR) or conditionally from SHR age 14 or 26 weeks. Elevated blood pressure in SHR aged 26 weeks was reduced by EH. Blood pressure in SHR aged 14 weeks was almost unaffected by EH and blood pressure went up in ten weeks old SHR. SP had a weaker action in comparison with EH. These results are in agreement with the hypothesis proposed by Oehme and co-workers [11-13] that SP can act as a regulatory peptide (="regulide").
The non-cleared influences of the sympathetic nervous system [sN] on structural reactions of SHR and on the direct cardiac effects of AII and the structural vascular behavior were investigated. In 67 spontaneously hypertensive rats (Okamoto-Aoki) and 55 normotonic Wistar rats (NR) the blood pressure behaviour, the structural vascular and organ reactions and the noradrenaline (NA) content of the myocardium were examined with an intact sympathetic nervous system as well as after its almost complete elimination by chemical sympathectomy with 6-hydroxy-dopamine (6-OH-DA). Moreover, the functional and structural responsiveness of the arterial vessels of sympathectomized animals to angiotensin II administrations was investigated. 6-OH-DA in the dosage applied, induces during its time of action in NR a smaller, in SHR a larger decrease of blood pressure and, presumably induced by intense NA-depletion of the myocardium, myocardial alterations. Despite extensive AII-induced alterations of the already early hypertrophically-hyperplastically changed vascular wall, the structural and functional responsiveness of the arterial vascular system was maintained even after sympathectomy, and the sensitivity of the SHR to AII remained. For maintaining hypertension, the cooperation of structural and functional influences is necessary, as is indicated by the reduction of blood pressure in sympathectomized SHR and its regular return to the daily initial values of normotonic animals under additional AII administration. Besides the vascular alterations contributing to the exacerbation of the hypertension, here the sNS is of essential importance. For obtaining a total pressure effect of AII the sNS obviously has not necessarily to be intact, though its activity state can influence the responsiveness of the arterial vascular system to AII. The reduction of the sympathicotonus by sympathectomy seems to have a protective effect on the development of AII-induced structural vascular alterations; in contrast to the myocardium in SHR, in which it induces an exacerbation and an increase in the AII-induced myocardial alteration. These findings obtained from rats are supposed to be important also for the essential hypertension in man. By maintaining the functional responsiveness of the arterial vascular system, antihypertensives which react with the different parts of the sNS cab become effective while structural alterations of the vascular wall can be influenced, too. The possibility of the simultaneous development of myocardial alterations should be taken into special consideration.
In 55 spontaneously hypertensive rats (SHR) (Okamoto/Aoki) and 63 normotensive Wistar rats (NR) receiving Angiotensin-II, hypertrophically-hyperplastically altered vessels of SHR were tested for their functional and structural reactivity and compared with the behaviour of the arterial vascular system at essential hypertension of man. After 5 days of treatment with 0.15 and 0.02 mg depot-Angiotensin II (A-II) SHR showed an increase in systolic and, with 0.15 mg A-II, even in diastolic blood pressure and bradycardia. At either A-II dosage, plasmatic vasculoses were found at the arterioles and small arteries both in SHR and similarly treated NR, though in higher frequency and in a larger quantity in SHR, as it was the case also with myocardial alterations. Although in the arterial vessels in SHR there developed already primary hypertrophically-hyperplastic wall alterations, A-II application led to functional and structural reactions. Consequently, an additional vasoconstrictor stimulus does not lead in SHR to a process comparable with essential hypertension in man, but merely to reversible, acute vasculopathies.