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Biomedical subjects

M L Watson

Publications and source records attributed to M L Watson.

At least 109 records · Page 6Linked to original sources
PubMed1984

Contribution of prostaglandins to the systemic and renal vascular response to frusemide in normal man.

In eight normotensive male volunteers indomethacin decreased both the peak urine flow rate and total sodium excreted within 1 h of an intravenous dose of frusemide. Resting effective renal plasma flow and glomerular filtration rate were unchanged by indomethacin, but the increase in both parameters after frusemide was inhibited. The early increase in plasma renin activity after frusemide was inhibited by indomethacin. Indomethacin decreased urinary excretion of PGE by 80% and the increase after frusemide was abolished. The urinary excretion of a metabolite of systemic PGI2 was unaltered in the 40-60 min period following frusemide. The early haemodynamic effects of frusemide are likely to be prostaglandin mediated, but there was no evidence of any change in systemic PGI2 synthesis after frusemide.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Endogenous prostacyclin synthesis is decreased during activation of the renin-angiotensin system in man.

Prostacyclin has been implicated as a mediator of renin release, whereas angiotensin II evokes prostaglandin I2 (PGI2) release from both vascular and nonvascular tissues in vitro. The physiological significance of these observations was assessed by measurement of an index of endogenous prostacyclin biosynthesis in human volunteers during varied activation of the renin-angiotensin system secondary to manipulation of dietary sodium. Excretion of the major urinary metabolite of prostacyclin in man, 2,3-dinor-6-keto-PGF1 alpha (PGI-M), fell from 295 +/- 51 to 176 +/- 35 (+/- SEM) ng g creatinine-1 (P less than 0.01) in 10 normal subjects when sodium intake was decreased from 150 to 10 meq/day. In five patients with primary hyperaldosteronism, PGI-M fell from 199 +/- 34 ng g creatinine-1 preoperatively to 120 +/- 26 pg/mg creatinine-1 after removal of the adenoma. In such patients, the reduction in PGI-M was associated with a significant increase in PRA. Thus, in both normal subjects and patients with hyperaldosteronism, PGI-M excretion fell rather than increased with activation of the renin-angiotensin system. This suggests that systemic biosynthesis of PGI2 is unrelated to renin release and that angiotensin II is unlikely to stimulate endogenous prostacyclin biosynthesis under these conditions in man.

Adenoma↗
PubMed1983

Systemic prostaglandin I2 synthesis is normal in patients with Bartter's syndrome.

Urinary excretion of 2, 3 dinor-6-keto-PGF1 alpha, a metabolite of prostacyclin (PGI2), was measured in 9 patients with Bartter's syndrome. The rate of excretion of this metabolite was normal in these patients during ingestion of both a normal and high dietary intake of potassium. This suggests that in Bartter's syndrome the rate of entry of PGI2 into the circulation is normal. Excessive systemic synthesis of PGI2 is therefore unlikely to be an explanation for either the vascular insensitivity to angiotensin II or the defect in platelet aggregation characteristic of the syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

The effect of sodium restriction during gestation of offspring brain development in rats.

Sodium restrictive diets are today often recommended to women experiencing the normal edema of pregnancy. This study explores some effects of dietary sodium restriction, imposed during pregnancy, on reproductive performance and brain development in resultant offspring. Pregnant Sprague-Dawley rats were fed diets containing either 0.173, 0.067, 0.040, or 0.022% sodium throughout gestation. All other nutrients in the diet were fed at levels in excess of NAS-NRC requirements. At parturition, litters were trimmed to four offspring and mothers fed Purina Rat Chow throughout lactation. Twenty-one days postpartum, offspring were killed and analyses of selected parameters of brain composition made. Rats fed the 0.040 and 0.022% were killed and analyses of selected parameters of brain composition made. Rats fed the 0.040 and 0.022% sodium containing diets during pregnancy consumed less feed, gained less weight, and exhibited altered fluid consumption patterns to rats ingesting the 0.173% sodium control diet. Mothers fed the two diets containing the lowest levels of sodium also had smaller litters, fewer live births, and more stillbirths per litter than control mothers. Birth weights and the number of offspring surviving the lactation period were less in the 0.040 and 0.022% sodium treatment groups. No offspring in the 0.022% sodium diet group survived the lactation period. Brain wet weight, dry weight, cholesterol, protein, and RNA content were decreased in offspring in the 0.040% sodium diet group.

Animals↗
PubMed1982

Role of prostaglandins in mediating excretion by the kidney of an intravenous infusion of sodium chloride in normal human subjects.

1. Normal male subjects were given a rapid infusion of 3 litres of sodium chloride solution (150 mmol/l) with or without pretreatment with indomethacin. 2. There was marked individual variability in the rate at which the infused sodium chloride solution was subsequently excreted which was not related to the urinary sodium excretion in the previous 24 h. 3. There was no relationship between urinary prostaglandin E excretion during the 24 h preceding the sodium chloride infusion and the rate at which different individuals subsequently excreted sodium and water. 4. Renal plasma flow was significantly higher during the sodium chloride infusion than in the post-infusion recovery period, both with and without pretreatment with indomethacin, although it was significantly lower during each period in subjects pretreated with indomethacin. 5. Urinary prostaglandin E excretion was significantly decreased after the infusion of sodium chloride solution. 6. Indomethacin slightly decreased the rate of excretion of sodium and water. 7. Prostaglandins have a role in, but are not the main determinants of, the excretion of an intravenous infusion of sodium chloride. 8. The results do not support the suggestion that prostaglandin E produced within the kidney, as indicated by urinary prostaglandin E excretion, exerts a natriuretic action.

Adult↗
PubMed1981

Effects of salt and water depletion on the early phase of hypertension in Goldblatt two-kidney hypertensive dogs.

1. Hypertension was induced in dogs by partial occlusion of one renal artery, the opposite kidney remaining intact, and the changes in blood pressure, plasma renin activity, aldosterone and prostaglandin E (PGE) were monitored. 2. Two days after induction of hypertension, the retained sodium and water were removed by haemodialysis and the animals were then maintained on a low dietary intake of sodium for the following 7 days. 3. Removal of the accumulated sodium and water had no immediate effect on blood pressure, but during the ensuring 7 days there was a small decrease in blood pressure, which again increased after re-institution of a normal sodium intake. 4. Plasma renin activity and aldosterone increased during development of hypertension and remained elevated during the period of sodium restriction. 5. Sodium and water retained during the development of hypertension was not responsible for the elevated blood pressure. 6. The concentration of PGE in arterial plasma and renal venous plasma from the unclamped kidney were unchanged during the study, although we have previously shown that in the absence of sodium depletion, PGE rises. 7. PGE released from the kidney may be important in mediating the excretion of sodium and water that is retained during the development of renal hypertension.

Aldosterone↗
PubMed1981

A comparison of the effects of prostaglandins E2 and I2 on renal function and renin release in salt-loaded and salt-depleted anaesthetized dogs.

Prostaglandin E2 (PGE2) and prostaglandins I2 (PGI2) were infused into the renal artery of either sodium-loaded or sodium-depleted dogs. Systemic blood pressure was decreased and arterial plasma renin concentration increased in the sodium-loaded dogs by infusion of PGI2 (1200 ng/min). Both compounds increased renal blood flow but PGE2 had a much more potent effect than PGI2 on increasing urine flow and sodium excretion. In the sodium-depleted dogs systemic blood pressure was significantly decreased and arterial plasma renin concentration increased by infusions of PGI2 (300 and 1200 ng/min) and PGE2 (300 ng/min). Both compounds stimulated urine flow and renal blood flow but PGE2 induced a much larger increase in sodium excretion than PGI2. PGI2 exerts its actions on renal function by inducing vasodilatation whereas PGE2 also has a direct action on tubular function.

Animals↗
PubMed1981

Renal interstitial cell granularity in dogs with renal hypertension.

Hypertension was induced in dogs by the partial occlusion of one renal artery. After 12 days of hypertension the interstitial cells in the medulla of kidneys from hypertensive animals were examined by electron microscopy, and the appearance compared with interstitial cells from normal dogs. The osmiophilic granules in the cells were classified into dark and light forms, and the numbers of each counted in at least 70 cells per kidney. It was not possible to quantify the number of interstitial cells in each renal medulla. The kidneys with partially occluded renal arteries had an increased total number of granules per cell (4.93 +/- 0.51) compared with normal kidneys (0.79 +/- 0.14), and the great majority of these were dark granules (95.3% and 79.5%, respectively). In contrast the contralateral untouched kidneys had a significantly reduced number of granules per cell (0.58 +/- 0.14), and only a small proportion of the total were dark granules (31.1%). The actual number of light granules per interstitial cell was significantly increased in the untouched kidney compared with normals.

Animals↗
PubMed1978

Fenfluramine, vitamin C and weight loss.

Forty-two female patients with refractory obesity completed a 20-week double-blind study during which they were given a diet designed to provide not more than 40 mg vitamin C and 1000 kcal (4.2 MJ) daily. Twenty-two of the patients took 600 mg of supplementary vitamin C daily and the remainder, a matched placebo. All were given their highest tolerated dose of fenfluramine up to a maximum of 160 mg daily. There was no significant difference in the mean weight loss of the two groups. This study fails to support the hypothesis that the anti-obesity effect of fenfluramine is influenced by the vitamin C intake.

Administration, Oral↗
PubMed1977

Plasma fenfluramine levels, weight loss, and side effects.

Fifty women with refractory obesity received fenfluramine for 20 weeks. Every two weeks details of weight change, drug dose, degree of anorexia, and any side effects were recorded and plasma was obtained for fenfluramine and norfenfluramine measurements. Of the 41 patients available for final analysis 26 achieved a maximum plateau dose of 160 mg/day. Plasma fenfluramine concentrations did not correlate with the degree of anorexia or with the incidence of side effects other than the severity of dream disturbance. There was a highly significant relation between weight loss and plasma fenfluramine and norfenfluramine concentrations and also between weight loss and the presence of sustained anorexia. Women who achieved mean plateau concentrations over 200 ng/ml lost a mean 8.8 kg while those with concentrations less than 100 ng/ml lost a mean of only 2.1 kg. When fenfluramine is prescribed in refractory obesity the dose should be increased stepwise until either satisfactory weight loss is achieved or troublesome side effects appear.

Adult↗