Biomedical subjects

A Barden

Publications and source records attributed to A Barden.

At least 37 records · Page 2Linked to original sources

PubMed1988

Effect of potassium supplementation on blood pressure and vasodilator mechanisms in spontaneously hypertensive rats.

1. Supplementation with 1% (w/v) KCl solution significantly attenuated the blood pressure rise with age normally observed in spontaneously hypertensive rats, resulting in a difference in blood pressure of 18 mmHg after 5 weeks. 2. Urinary 6-keto-prostaglandin F1 alpha (the stable hydrolysis product of prostacyclin) and kallikrein excretion were significantly elevated in rats receiving potassium. 3. No difference was observed in sodium excretion during the initial days of potassium supplementation; however, the potassium-supplemented animals excreted relatively more sodium over the 5 week period. 4. Plasma renin activity was significantly reduced in those animals receiving potassium after 5 weeks. 5. It is proposed that a combination of increased systemic and/or renal prostacyclin and kallikrein synthesis may, in combination with reduced renin activity, contribute to the attenuation of blood pressure in potassium-supplemented spontaneously hypertensive rats.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Effect of dietary fish oils on the formation of leukotriene B4 and B5, thromboxane and platelet activating factor by rat leukocytes.

1. This study investigates the effect of dietary eicosapentaenoic acid (EPA), in the form of 'Max EPA' fish oil, on leukotriene B4 (LTB4) production in ionophore-stimulated rat leukocytes. Male Wistar rats (200-250 g) were fed for 3 weeks on a synthetic chow supplemented with either 10% by weight Max EPA oil or a coconut oil/safflower oil mixture. 2. The EPA-rich diet significantly increased the EPA content of leukocyte phospholipids and decreased the arachidonic acid level by 35% (P less than 0.001) compared with the control diet. 3. The concentration of leukotrienes in the ionophore (A23187) stimulated leukocytes was measured by reverse-phase HPLC using prostaglandin B2 as the internal standard. The EPA-supplemented diet caused a 50% decrease in LTB4 production (P less than 0.001) and a concomitant increase in the formation of the biologically less active LTB5 compared with the control diet. The amount of LTB4 and LTB5 produced by stimulated leukocytes closely resembled the changes in arachidonic acid and EPA content of leukocyte phospholipids. 4. Thromboxane B2 (TxB2) production in stimulated leukocytes from the EPA-fed animals was also decreased compared with the control group. 5. Although the formation of platelet activating factor by stimulated leukocytes was not altered by dietary treatment, the ability of an EPA-rich diet to decrease LTB4 and TxB2 production suggests that these diets may attenuate leukocyte activity and have useful anti-inflammatory effects.

Animals↗

PubMed1987

Potassium supplementation lowers blood pressure in spontaneously hypertensive rats--relationships with urinary prostaglandins and renin.

Supplementation with 1% KCl significantly attenuated the blood pressure rise normally observed in SHR's with increasing age. Urine volume and urinary excretions of sodium, potassium and 6-keto-PGF1 alpha were significantly elevated in those animals receiving potassium. Plasma renin activity measured at the end of the study was significantly reduced in potassium supplemented animals compared to controls.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

Increases in urinary kallikrein activity and prostanoid synthesis after dietary potassium supplementation.

1. To determine whether increasing dietary potassium alters kallikrein activity or prostaglandin synthesis, 77 women participated in a 3 week screening to assess their dietary potassium intake. Forty-four normotensive women whose dietary potassium was less than 60 mmol/day were allocated randomly to one of two groups who took either 80 mmol/day KCl (Slow-K, Ciba Geigy) or matching placebo for the first or second of two 4 week periods. 2. Significant increases in urinary kallikrein excretion (P less than 0.01), and urinary 6-keto-PGF1 alpha (P less than 0.01) were observed during potassium supplementation. These changes occurred without alterations in urine volume or sodium excretion. 3. It is suggested that potassium-induced changes in urinary 6-keto-PGF1 alpha may reflect increased renal and possibly vascular synthesis of prostacyclin. These increases may be mediated by increased plasma potassium stimulating kallikrein synthesis, leading to bradykinin-induced activation of phospholipase A2. Enhanced kallikrein/kinin and prostacyclin formation could contribute to the blood pressure lowering effect of potassium reported in hypertensive subjects.

6-Ketoprostaglandin F1 alpha↗

PubMed1986

Nutrient intake, blood pressure, serum and urinary prostaglandins and serum thromboxane B2 in a controlled trial with a lacto-ovo-vegetarian diet.

Fifty-nine healthy omnivores volunteered for a randomized crossover trial with a lacto-ovo-vegetarian (L-O-V) diet. Twenty-one 1-day diet records were kept throughout the project as a means of assessing food and nutrient intakes, and samples of serum and urine were assayed to evaluate change in prostanoid metabolism. While on the L-O-V diet subjects ate more vegetable protein, wholegrain cereals, polyunsaturated oils, fruits and vegetables, and avoided eating meat, fish or poultry. The L-O-V diet contained significantly more polyunsaturated fatty acids, fibre, vitamin C, vitamin E, magnesium, calcium and potassium, and less total protein, saturated fat, monounsaturated fat and vitamin B12 than the control omnivore diet. Changes in nutrient intakes were subjected to principal components analysis to identify dimensions of change in nutrient intakes. Three Factors accounted for 83% of the total variation in dietary intake. Blood pressure changes were significantly and negatively (F = 17.4, P less than 0.001 for systolic; F = 6.09, P = 0.02 for diastolic pressure) related to individual scores for only one Factor--that representing an increase in intake of polyunsaturated fat, fibre, vitamin C, vitamin E, calcium and magnesium, and a fall in intake of protein and vitamin B12. Blood pressure changes were unrelated to change in body weight or sodium intake. Serum and urinary prostanoids were not affected by eating the L-O-V diet.

Blood Pressure↗

PubMed1985

Onset of changes in phospholipid fatty acid composition and prostaglandin synthesis following dietary manipulation with n-6 and n-3 fatty acids in the rat.

A synthetic diet preparation supplemented with 10% by weight of either safflower oil, hydrogenated coconut oil containing 3% safflower oil, or 'max EPA' fish oil was fed to rats over a 8-week period. Serial measurements of serum fatty acids, serum thromboxane B2 and urinary prostaglandin excretion were taken during the treatment period to assess the rate of change in fatty acid composition and prostaglandin synthesis following dietary manipulation. There was no significant change in weight gain between the dietary groups during the treatment period. Significant changes in serum fatty acids occurred within 48 h of treatment, with the 'max EPA' oil group having arachidonic acid levels reduced by 23% (P less than 0.01) compared to the coconut oil group. Conversely, rats fed safflower oil had an 18% enhancement of arachidonic acid during the same time period. Whole blood synthesis of thromboxane B2 was significantly depressed (P less than 0.01) after 48 h in rats fed 'max EPA' oil compared to the safflower oil or coconut oil groups. This suppression reached a maximum of 65% (P less than 0.001) after 7 days of dietary 'max EPA' oil treatment. The safflower oil and coconut oil-fed groups showed the same levels of serum thromboxane B2 production over the treatment period. Urinary excretion of both 6-ketoprostaglandin F1 alpha and prostaglandin E2 varied significantly (P less than 0.01) between the groups after 7 days of dietary treatment. Rats fed 'max EPA' oil had depressed urinary prostanoid excretion compared to the safflower and coconut oil groups which remained very similar to each other. After the 8-week treatment period rats were killed and the phospholipid fatty acid composition and prostaglandin-generating capacity of platelets, aorta and renal tissue was examined. Prostanoid production by kidney cortex and medulla and segments of aorta was consistently suppressed in rats fed 'max EPA' oil. These observations correlated well with changes in the phospholipid fatty acid profiles in these tissues. This study shows rapid changes in serum fatty acids and thromboxane B2 generation following dietary manipulation, while changes in urinary excretion or prostanoid metabolites occur only after a longer time period.

Animals↗

PubMed1985

Influence of age, sex and potassium excretion on urinary prostaglandins in children.

Measurement of urinary 6-ketoprostaglandin (PG) F1 alpha and PGE2 excretion in 83 healthy children, aged 5-15 years, revealed that supervised 4 h urine collections under mild water diuresis provided more consistent results than overnight 12 h urine collections. Males had higher urinary excretion of 6-keto-PGF1 alpha but not of PGE2 compared with females. Urinary potassium was related to 6-keto-PGF1 alpha in both 4 and 12 h urine collections and urinary sodium to 6-keto-PGF1 alpha in 4 h collections only. In the sexes combined multiple regression analyses revealed age as the only significant influence on prostanoid excretion (P = 0.001). Thus age and sex and dietary potassium intake need to be considered in studies of urinary prostanoids in children.

6-Ketoprostaglandin F1 alpha↗

PubMed1985

Renal prostanoids after unclipping the denervated one-kidney, one-clip hypertensive rat.

The contribution of the renal nerves in maintaining blood pressure and modulating renal prostanoid synthesis was examined in established (less than 8 wk in duration) one-kidney, one-clip (1K,1C) hypertension in the rat. Systolic blood pressure was measured for 7 days after renal denervation, at which time the renal artery clip was removed. Twenty-four-hour urinary excretion of PGE2 and 6-keto-PGF1 alpha (stable degradation product of PGI2) was determined before and after denervation and unclipping. Compared with sham-denervated rats, denervation (n = 15) resulted in a small but significant fall in blood pressure (from 216 +/- 4 to 182 +/- 4 mmHg after 48 h) and an increase in urinary 6-keto-PGF1 alpha (from 31 +/- 4 to 43 +/- 5 ng/24 h after 24 h). There was no change in PGE2 excretion. Seven days after surgery, blood pressures were similar in denervated (202 +/- 4 mmHg) and sham-denervated (211 +/- 5 mmHg) rats and fell to a similar extent 24 h after unclipping (142 +/- 3 and 147 +/- 4 mmHg, respectively). Urinary 6-keto-PGF1 alpha increased from 25 +/- 5 to 74 +/- 11 in denervated and 21 +/- 2 to 72 +/- 9 ng/24 h in sham-denervated rats in the 24 h after unclipping. PGE2 excretion increased approximately twofold over this period. These findings indicate that the renal nerves have only a minor role in established hypertension in the 1K,1C rat and that the reversal of hypertension and stimulation of renal prostanoid synthesis following unclipping is not dependent on neural mechanisms.

6-Ketoprostaglandin F1 alpha↗

PubMed1984

Validation of the direct radioimmunoassay of prostanoids in serum and kidney.

Results obtained from radioimmunoassay (RIA) at various stages of sample processing were compared in order to determine the degree of purification necessary to estimate levels of prostaglandins (PG) and thromboxane B2 (TXB2). In serum, TXB2 levels were closely comparable when assayed directly or after organic extraction and thin layer chromatography (TLC). Although concentrations of 6-keto-PGF1 determined by both methods were correlated, levels were significantly overestimated by the direct method. PGE2 and 6-keto-PGF1 alpha levels measured directly in acetone extracted kidney homogenate were almost identical with kidney homogenates taken through the full extraction procedure and TLC. After indomethacin treatment serum 6-keto-PGF1 alpha and PG levels in kidney homogenate assayed directly were markedly different from extracted values. Thus direct RIA of samples is reliable when prostanoid levels are high in relation to interfering substances, as with serum TXB2 and kidney homogenate 6-keto-PGF1 alpha and PGE2, but not for serum 6-keto-PGF1 alpha or following PG inhibition.

6-Ketoprostaglandin F1 alpha↗

PubMed1984

An inhibitory effect of dietary polyunsaturated fatty acids on renin secretion in the isolated perfused rat kidney.

The influence of dietary modification of polyunsaturated fatty acids (PUFA) on renin secretion, renal vascular tone and prostanoid excretion was studied in isolated perfused rat kidneys under basal conditions and in response to angiotensin II. After a four-week regimen of diets enriched with safflower oil, linseed oil or saturated fat, providing 20% of total energy intake (20 energy %), the animals which were fed linseed oil showed a significant fall in the proportion of arachidonic acid in renal phospholipids and a reduction in urinary prostaglandin excretion. In comparison with the other dietary groups, linseed oil feeding also resulted in a consistently lower renal vascular tone with increasing doses of angiotensin II. Under basal conditions both the PUFA-fed groups had significantly lower renal venous renin secretion rates relative to the saturated fat-fed control group. Infusion of angiotensin II (10 ng/min) suppressed renin secretion and abolished significant differences between the groups. As both the control group and the safflower oil group excreted similar levels of urinary prostaglandins, these results suggest that dietary enrichment with 20 energy % PUFA alters renin secretion by a prostaglandin-independent mechanism and that this may contribute to the lower blood pressures observed in these animals compared with the saturated fat-fed control group.

6-Ketoprostaglandin F1 alpha↗

PubMed1983

Radioimmunoassay of prostaglandins and thromboxane B2 in extracted and unextracted urine and serum using an iodinated ligand.

A comparison of radioimmunoassay (R.I.A.) for 6-keto PGF 1 alpha, PGE2 and TXB2 using 125I-histamine ligands and tritiated tracers showed a 7 to 10 fold increase in sensitivity for the 125I derivative, with a resultant reduction in antisera requirements by 80%. Study of the effect of purification of biological samples by organic extraction and thin layer chromatography showed that for human and rat urine, and urine from perfused rat kidneys, direct R.I.A. of unextracted samples gave substantially higher estimates of PGE2, 6-keto PGF1 alpha and TXB2 than R.I.A. purified material. Indomethacin pre-treatment reduced the levels estimated in both extracted and unextracted samples; the results indicating that the higher estimates obtained by direct assay were due to a combination of PG/TXB2 metabolites and non-specific interference. In serum from incubated human blood, estimated 6-keto PGF1 alpha and PGE2 levels were significantly higher by direct R.I.A. than after extraction, whereas TXB2 levels were similar. Thus purification procedures are unnecessary when high serum TXB2 levels are being measured by R.I.A. with relatively specific antisera.

Animals↗

PubMed1983

Release of prostaglandins during reversal of one-kidney, but not two-kidney, one clip hypertension in the rat.

Changes in systolic blood pressure and urinary excretion of PGE2 and 6-keto PGF1 alpha 24 h after removing the renal artery clip were compared in one-kidney and two-kidney, one clip Goldblatt hypertension in the rat. Unclipping the one-kidney rat returned blood pressure to normotensive levels within 24 h and was associated with a substantial increase in urinary PGE2 and 6-keto PGF1 alpha. Although hypertension was also completely reversed in the two-kidney model there was no significant change in urinary prostaglandin excretion. Prior treatment with indomethacin (6.0 mg/kg) markedly reduced urinary prostaglandins after clip removal in both forms of hypertension but attenuated the fall in blood pressure in the one-kidney model only. There were no significant changes in urinary kallikrein activity following unclipping. It is suggested that in the one-kidney, one clip rat prostaglandins are released as the result of exposing the unclipped kidney to elevated arterial pressure and that these contribute to the subsequent fall in blood pressure.

Animals↗

PubMed1982

Phosphorylation of ribosomal proteins during the cell cycle of Physarum polycephalum.

Physarum polycephalum has been used as a model system to study the phosphorylation of ribosomal proteins during the cell cycle. The results showed that the phosphate content of S3, the major ribosomal phosphoprotein in this organism, was constant during all phases of the cell cycle. No additional ribosomal phosphoproteins were observed. These results differ significantly from those reported earlier by Rupp, R.G., Humphrey, R.M. and Shaeffer, J.R. (Biochim. Biophys. Acta (1976) 418, 81-92) and suggest that the use of thymidine or hydroxyurea to synchronize cell population may affect the phosphorylation of ribosomal proteins. The results are discussed in relation to protein synthesis and cAMP level during the cell cycle.

Animals↗

PubMed1982

Phosphorylation of ribosomal proteins S3, L1 and L24 during spherulation in Physarum polycephalum.

The phosphate content of ribosomal proteins S3, L1 and L24 has been determined in the course of spherulation of Physarum polycephalum. The major phosphoprotein, S3, was completely dephosphorylated after 4 h of differentiation. The phosphate content of L1 and L24 was not altered during the differentiation. The cellular level of ATP remained constant for at least 5 h. A 3-fold reduction of cyclic AMP concentration occurred in the first hour, followed by a slow increase to a final value of twice the level observed in growing cells. The results showed that the phosphorylation of ribosomal proteins is regulated by at least two different mechanisms and that the dephosphorylation of S3 is not induced by a lack of cellular ATP. Although cyclic AMP might trigger the dephosphorylation of S3, the phosphate content of this protein remained at a very low value even when the cellular concentration of cyclic AMP rose significantly. Since the polysome level remains constant during the first 24 h of spherulation, the phosphorylation of S3 is not necessary for active protein synthesis and the phosphorylation of L1 and L24 is not involved in ribosome inactivation, which occurs after 24 h.

Adenosine Triphosphate↗

PubMed1982

Effect of alpha-adrenergic stimulation on prostacyclin and renin release in the rat kidney.

The relationship between renin secretion and PGI2 production, in response to intrarenal infusion of norepinephrine, was examined in the isolated perfused rat kidney. Infusion of norepinephrine in a dose which caused substantial vasoconstriction (100 ng/min), markedly increased urinary excretion of 6-keto PGF1 alpha, the stable derivative of PGI2, without significantly altering renin secretion measured in the effluent perfusate. No change in urinary 6-keto PGF1 alpha occurred when vasoconstriction was prevented by infusing the alpha-adrenoceptor blocking drug phenoxybenzamine (2 x 10(3) ng/min) alongside norepinephrine (100 ng/min). However, under these conditions there was marked stimulation of renin secretion which, as has been demonstrated previously, is mediated by a beta-adrenoceptor. There were significant increases in urine flow rates during both vasoconstrictor and non-vasoconstrictor infusions. These findings clearly indicate that in the rat kidney prostacyclin production and renin release in response to norepinephrine are dissociated.

6-Ketoprostaglandin F1 alpha↗

PubMed1981

Dissociation of beta-adrenergic stimulation of renin secretion and prostacyclin synthesis in the rabbit kidney.

The effect of inhibition of prostaglandin (PG) synthesis with indomethacin on basal and isoproterenol-stimulated renin secretion was examined in the isolated perfused rabbit kidney. 6-keto PGF1 alpha' the stable metabolite of prostacyclin, was measured in urine by radioimmunoassay using 125I labelled histamine coupled to 6-keto PGF1 alpha as ligand. The level in urine, prior to isolation and perfusion of the kidney, was 10.7 +/- 5.6 ng/min, and this was reduced to 0.32 +/- 0.25 ng/min (P less than 0.05) in rabbits treated with 2.0 mg/kg of indomethacin. Renin release was markedly stimulated by intrarenal infusion of isoproterenol (0.1 microgram/min) but urinary 6-keto PGF1 alpha did not change. These responses were not affected by indomethacin treatment. Renal perfusion pressure, perfusate flow rate and consequently renal vascular resistance, remained relatively constant during the course of perfusion and were unaltered by indomethacin treatment. These results therefore do not support a role for PGs, and in particular prostacyclin, in the renin response to beta-adrenergic stimulation with isoproterenol.

6-Ketoprostaglandin F1 alpha↗

PubMed1980

Effect of propranolol on the renin response to frusemide in man.

The response of plasma renin activity (PRA) to frusemide, 40 mg given intravenously, was examined before and after oral propranolol 160 mg daily for seven days in normal and hypertensive subjects. Although basal PRA was reduced in many cases, the increase following frusemide was essentially unaltered by propranolol therapy. Evidence is presented that adequate beta adrenoceptor blockade was attained in these studies. Increasing the dose of propranolol to 240 mg daily for seven days in two subjects did not alter renin responsiveness to frusemide. Stimulation of renin release by oral frusemide, examined in one subject, was also unaltered by propranolol therapy. These findings indicate that enhancement of renin activity associated with diuretic use may not be prevented by concurrent propranolol administration. Limitation of the hypotensive action of combined beta blocker-diuretic therapy can therefore be expected. The fact that the renin stimulating effect of frusemide is preserved during beta blockade indicates that this procedure can be used in the investigation of hypertension even in those patients in whom discontinuation of beta blocking treatment may be undesirable.

Adult↗

PubMedDate not supplied

Effect of beta-adrenoreceptor blockade on the renin response to acute natriuresis.

1. The response of plasma renin activity to frusemide 40 mg given intravenously, was examined before and after oral propranolol 160 mg daily for 7 days in normal and hypertensive subjects. 2. Although basal renin levels were often reduced, the increase following frusemide was essentially unaltered by propranolol therapy. 3. These findings indicate that enhanced renin activity associated with diuretic use may not be prevented by concurrent propranolol administration. Limitation of hypotensive action of combined beta-blocker diuretic therapy can therefore be anticipated. 4. Preservation of the renin stimulatory effect of frusemide during beta blockade confirms the value of this procedure in the investigation of mineralocorticoid and renovascular hypertension were discontinuation of treatment may be undesirable.

Adrenergic beta-Antagonists↗