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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The object of this study was to develop an assay for platelet activating factor (PAF) in rat plasma, and to utilise this to determine the effects of dietary fish oil on PAF in normotensive and spontaneously hypertensive rats. Measurement of platelet activating factor in blood plasma has proved difficult because of its rapid hydrolysis in vivo to lyso PAF. We describe here a method based on the prior acetylation of lyso PAF extracted from plasma to PAF before bioassay using 14C-serotonin labelled platelets. The active material found in acetylated plasma extracts was characterized as PAF by its chromatographic mobility, the action of phospholipases A2, C and D and by cross-desensitization studies with rabbit platelets. Rats fed dietary fish oil ('max EPA') had significantly decreased plasma lyso-PAF levels compared to control animals fed hydrogenated coconut oil (HCO). Serum thromboxane B2 (TXB2) levels were also significantly lower in animals fed the 'max EPA' diet. Spontaneously hypertensive rats (SHR) had significantly lower plasma lyso-PAF levels than their normotensive Wistar Kyoto (WKY) controls maintained on the same diets. It is proposed that dietary alterations in PAF synthesis may influence platelet behaviour in addition to the well described effects of dietary fish oil on the proaggregatory prostanoid TXA2. Rat strain differences in lyso-PAF synthesis occur, but are unlikely to be related to the maintenance of hypertension in SHR.
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PMID:Dietary fish oils reduce plasma levels of platelet activating factor precursor (lyso-PAF) in rats. 370 10

The interaction of dopamine and angiotensin II (AII) on blood pressure and heart rate was studied in rats. The influence of reserpine pretreatment and vagotomy was also studied. Inbred rats anesthetized with urethane received intravenous (i.v.) doses of 50, 100, 200, or 400 micron g (per 100 g body weight) of dopamine HCI, before and after a single i.v. dose of 0.025 micron g of AII. The same doses of dopamine were tested in vagotomized rats and in rats pretreated with reserpine. The effect of dopamine alone on blood pressure was biphasic, since 16 of 38 rats showed an early fall followed by a later rise. The early fall decreased significantly with the dose and was absent with the highest dose tested (400 micron g). The late rise was observed in all experiments, and it increased significantly with the dose. Parallel to hypotension, a decrease of heart rate was observed, but both phenomena appeared not to be linked by a sauce-effect relationship. Vagotomy prevented both hypotension and bradycardia induced by dopamine. Angiotensin II inhibited the early fall and increased the late rise of blood pressure induced by dopamine but had no effect on the bradycardia. Reserpine retreatment prevented the hypotensive and enhanced the hypertensive response to dopamine, and in this situation dopamine induced cardiac arrhythmia. The interaction between dopamine and AII is inhibited by pretreatment with reserpine. The early hypotensive phase and bradycardia caused by dopamine appeared to be the consequence of a vagal reflex.
Hypertension
PMID:Enhancement of blood pressure response to dopamine by angiotensin II. 729 33

The effect of dietary fish oils on development of hypertension and vascular response in vitro were studied in rats and a primate. Dietary fish oils (MaxEPA and an n-3 ethyl ester concentrate of higher EPA and DHA content) were administered to spontaneously hypertensive (SHR), stroke-prone spontaneously hypertensive (SHR-SP) and a backcross of SHR and Wistar Kyoto (SHR/WKY) rats from 4-16 weeks of age. Blood pressure was monitored during the feeding period and vascular responses measured in the aorta and mesenteric vascular bed in vitro. Depending on the strain of rat used and the composition of the fish oil the attenuation in blood pressure was 10-26 mmHg. Fish oils attenuated the response mediated by sympathetic nerve stimulation or intralumenal norepinephrine in the perfused mesenteric vascular bed preparation from the SHR. This attenuation was more pronounced for fish oils enriched with eicosapentaenoic acid and docosahexaenoic acid and was more prominent in the SHR and SHR/WKY backcross than it was in the SHR-SP. Prostanoid synthesis or nitric oxide modulation of alpha-adrenoceptor responses were shown not to be involved in the attenuation of vascular responses produced by fish oil. The maximum contraction of aortic ring preparations in response to norepinephrine (NE) was significantly smaller in SHR than WKY rats fed olive oil and for SHR rats maintained on fish oils the contraction was close to WKY olive oil values. Evidence was obtained also for a modulation of vasoconstrictor responses by dietary fish oils in the perfused mesenteric bed of the marmoset monkey.
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PMID:Fish oils modulate blood pressure and vascular contractility in the rat and vascular contractility in the primate. 767 Jun 52

The present study was designed to assess whether a specific endothelin A (ETA) receptor antagonist, FR139317, affects the progression of lupus nephritis and affects transcription of mRNA for extracellular matrix (ECM) components, metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP)-1, and accumulation of ECM proteins in the renal cortex of NZB/W F1 mice. mRNA levels for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, heparan sulfate proteoglycan (HSPG), MMP-1, -2, -3, and TIMP-1 increased significantly as nephritis progressed in NZB/W F1 mice. At 48 weeks of age, the levels of mRNA for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, HSPG, MMP-1, -2, -3, and TIMP-1 were increased by 5.6- (P < 0.001), 3.6- (P < 0.01), 6.8- (P < 0.001), 5.2- (P < 0.001), 5.0- (P < 0.001), 6.0- (P < 0.001), 7.6- (P < 0.001), 4.2- (P < 0.01), 8.2- (P < 0.001), and 15.2-fold (P < 0.001), respectively, in the renal cortex of NZB/W F1 mice compared to NZW mice. Immunofluorescence microscopy showed that the accumulation of collagens I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice increased markedly with the progression of nephritis. At 20 weeks of age, NZB/W F1 and NZW mice were divided into two groups that received either FR139317 or its vehicle (saline) intraperitoneally, daily, for 28 weeks. The development of histological lesions, proteinuria, hypertension, accumulation of collagens I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice were suppressed by FR139317 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a specific endothelin A receptor antagonist on murine lupus nephritis. 772 34

Increased vascular collagen content is a major feature of pulmonary vascular remodeling. The functional role of excess collagen in decreasing pulmonary vascular compliance has not been established. We determined whether there was a correlation between hydroxyproline content of rat pulmonary artery segments and elastance (EPA) of the pulmonary artery bed during development of hypoxic pulmonary hypertension (10% O2, 10 d) and normoxic recovery. EPA was measured by air-filled pressure-volume curves. After 10 d of hypoxia, hydroxyproline content increased approximately 2-fold in large segments (1,200-250 microns in diameter) but not significantly in small segments (> 250 microns). Elastance increased from 87 +/- 6 (SEM) to 145 +/- 8 mm Hg/ml (p < 0.05) within 5 d of hypoxia and returned to control value 3 wk after recovery. There was a correlation between collagen content and EPA in large segments during development of hypertension; no correlation was found during recovery from hypoxia. The ratio of hydroxyproline to total protein was unchanged in large segments after recovery from hypoxia but was increased in small segments after recovery. We conclude that increased collagen in large pulmonary arteries directly influences EPA during the development of hypoxic pulmonary hypertension.
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PMID:Excess collagen in hypertensive pulmonary arteries decreases vascular distensibility. 817 73

Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids regarded as candidates for cardioprotective actions. At low dietary intakes (0.4-1.1% of energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited ischaemia-induced cardiac arrhythmias. At intakes of 3.9-10.0%en, docosahexaenoic acid was more effective than eicosapentaenoic acid at retarding hypertension development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane-like vasoconstrictor responses in aortas from SHR. In stroke-prone SHR with established hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the development of salt-loading induced proteinuria but eicosapentaenoic acid alone was ineffective. The results demonstrate that purified n-3 polyunsaturated fatty acids mimic the cardiovascular actions of fish oils and imply that docosahexaenoic acid may be the principal active component conferring cardiovascular protection.
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PMID:The cardiovascular protective role of docosahexaenoic acid. 874 Nov 70

Efforts in Finland to implement the recommended non-pharmacological and pharmacological principles for the control of hypertension, stroke and ischaemic heart disease have been accompanied by an approximately 10 mm Hg fall in the population average of diastolic blood pressure, and about 60% decrease in deaths from both stroke and ischaemic heart disease among 30-59-year-old men and women from 1972 to 1992. Adherence to antihypertensive drug therapy has been quite good. However, the drug treatment does not seem to account for more than 5-6% of the observed fall of blood pressure, and 10-15% of the decrease in deaths from strokes and ischaemic heart disease. There has been no overall adherence to several non-pharmacological recommendations, and marked increases in the intake of alcohol, obesity among men, and smoking among women have been observed. However, the population adherence to recommendations to decrease the intakes of sodium and saturated fats, and to reduce the sodium-to-potassium ratio and the saturated-to-unsaturated fat ratio, has been good. These dietary changes appear to account for a major part of the fall of blood pressure and the decrease in the cardiovascular diseases. Currently a rapid further population-wide decrease in the dietary sodium-to-potassium ratio is taking place, due to a decrease in the use of salt and replacement of common salt by a novel sodium-reduced, potassium-, magnesium-, and l-lysine HCI-enriched salt, both in home kitchens and in the food industry.
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PMID:Adherence to and population impact of non-pharmacological and pharmacological antihypertensive therapy. 896 92

The purpose of the present study was to investigate the effect of a concentrated preparation (EPA 30) containing eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) on the limiting desaturation steps of the polyunsaturated fatty acid biosynthesis in spontaneously hypertensive rats (SHR). Adult SHR were divided into two groups: one group received a standard diet, and the experimental group the standard diet including 0.8% of EPA30 for 9 weeks. Blood pressure was measured at the end of the diets. The desaturase activities and fatty acid composition were determined in isolated hepatocytes. The blood pressure did not decrease in the experimental group. The desaturated products of the n-6 family (gamma-linolenic acid, 18:3 n-6 and arachidonic acid, 20:4 n-6) were lowered in the EPA30 group, when their respective substrates (18:2 n-6 and 20:3 n-6) were increased. EPA and DHA were higher in the experimental group delta 6 n-3, delta 6 n-6 and delta 5 n-6 desaturase activities were depressed approximately 20% in the EPA30 group. EPA30 being an active nutrient on the EFAs cascade, increasing the level of PG3 precursors and decreasing the level of PG2 precursors, favourable conditions have been established to reduce hypertension. The underlying mechanism related to the regulation of desaturase activities by these fatty nutrients remains to be elucidated.
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PMID:Fatty acid metabolism, pharmacological nutrients and hypertension. 920 10

The objective of this study was to determine the effect of ethyl eicosopentate (EPA-E) on local cerebral blood flow (1-CBF) and local glucose utilization (1-CGU) in specific regions of the brain in stroke-prone spontaneously hypertensive rats (SHRSP). EPA-E (100 mg/kg body weight) or saline was orally administered to 8-week-old SHRSP. L-CBF and 1-CGU in the EPA-E-treated, saline-treated, and 8-week-old control rats were measured autoradiographically using 14C-iodoantipyrine and 14C-deoxyglucose (Sakurada's and Sokoloff's methods). The 1-CBF of the saline-treated group decreased significantly with age in all areas measured. EPA-E treatment alleviated the age-dependent decrease in 1-CBF in all areas, especially those in the basal ganglia. The 1-CGU of the saline-treated group did not change with age, however EPA-E treatment increased 1-CGU in all areas measured, though the changes were not significant. EPA-E ameliorated the decrease in cerebral blood flow and improved glucose metabolism in SHRSP suffering from severe hypertension. These results suggest that EPA-E may be useful in the prevention of stroke.
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PMID:Effect of long-term administration of ethyl eicosapentate (EPA-E) on local cerebral blood flow and glucose utilization in stroke-prone spontaneously hypertensive rats (SHRSP). 925 29

The present study was performed to characterize structurofunctional alterations of preglomerular vessels during chronic angiotensin II (Ang II)-induced hypertension (Ang II group: 400 ng x kg[-1] x min[-1], 10 days) and to assess the role of endothelin-1 in rats receiving Ang II and the mixed receptor antagonist bosentan (Ang II+B group: 30 mg x kg[-1] x d[-1], 10 days). Systolic blood pressure rose by 56+/-3 and 54+/-6 mm Hg in Ang II and Ang II+B rats, respectively. Albuminuria increased similarly in both Ang II-treated groups, reflecting glomerular barrier dysfunction. Preglomerular vessels were isolated after HCI maceration and comprised arcuate arteries and their branches, interlobular arteries (ILA), and afferent arterioles (AA). In the Ang II group, focal vascular lesions affected 36+/-6%, 20+/-5%, and 4+/-1% of arcuate arterial branches, ILA, and AA, respectively. They were characterized by 74% increased media thickness and accumulation of Sudan black-positive (SB+) lipid droplets, and media cell proliferation was documented through immunohistochemistry. The occurrence of SB+ lesions was strikingly reduced with bosentan. Autoregulatory responses (AR) were assessed along ILA and AA with the use of blood-perfused juxtamedullary nephron preparations. AR were elicited by raising blood perfusion pressure from 60 to 160 mm Hg and quantified through videomicroscopy as pressure-induced constrictions. AR were inhibited in Ang II-treated rats along ILA and AA; Ang II-induced AR changes were prevented by bosentan. Maximal relaxation induced by Mn2+ revealed equal basal tone in Ang II-treated, Ang II+B-treated, and control vessels. Chronic Ang II-induced hypertension is therefore associated with the development of SB+ lesions and selective impairment of AR in juxtamedullary nephrons. Endothelin-1 likely mediates the structurofunctional alterations of preglomerular vasculature during Ang II hypertension.
Hypertension 1997 Dec
PMID:Bosentan prevents preglomerular alterations during angiotensin II hypertension. 940 91


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