Biomedical subjects
P F Semple
Publications and source records attributed to P F Semple.
Is the 'sodium index' a useful way of expressing clinical plasma renin, angiotensin and aldosterone values?
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Bromocriptine: lack of effect on the angiotensin II and aldosterone responses to sodium deprivation.
Five normal subjects took a low sodium diet for four days on two occasions, one with and one without added bromocriptine 2.5 mg three times a day by mouth. Daily measurements of urinary electrolytes and the concentrations of plasma renin (PRC), angiotensin II (AII), aldosterone, 18-hydroxycorticosterone, cortisol, electrolytes and prolactin were made in both phases of the study. Deprivation of sodium without bromocriptine resulted in progressive and highly significant increases in the plasma concentration of aldosterone from 230 +/- 50 to 418 +/- 44 (SEM) pmol/l, 18-hydroxycorticosterone from 627 +/- 138 to 1420 +/- 478 pmol/l, PRC from 108 +/- 38 to 166 +/- 14 muU/ml and AII from 16 +/- 3 to 29 +/- 4 pmol/l. Similar changes were found during bromocriptine administration despite suppression of prolactin secretion. Sodium deprivation together with bromocriptine resulted in increases in the plasma concentrations of aldosterone from 230 +/- 47 to 416 +/- 72 pmol/l, 18-hydroxycorticosterone from 630 +/- 99 to 1629 +/- 552 pmol/l, PRC from 105 +/- 12 muU/ml and AII from 14 +/- 3 to 26 +/- 5 pmol/l. Plasma cortisol did not change either in response to sodium deprivation or bromocriptine. Mean cumulative negative sodium balance was 101 +/- 14 mmol on bromocriptine and 118 +/- 14 mmol in the control period. We conclude that prolactin is not necessary for the steroidogenic response to sodium deprivation in man.
[des-Asp1]angiotensin II in the dog: blood levels and effect on aldosterone.
Circulating levels of [des-Asp1]angiotensin II ([des-Asp1]-AII), angiotensin II (AII), and aldosterone were measured in five conscious beagle dogs before and during iv infusion of [des-Asp1]AII at rates of 3, 6, 12, and 24 ng/kg/min. The animals were studied after 4 days on a normal sodium and potassium diet and again after a period of sodium depletion accomplished by iv furosemide (2-5 mg/kg) and 4 days of low sodium diet (2-5 mmol/day). Compared to the normal sodium diet, sodium depletion resulted in increases in the plasma levels of aldosterone from 10 +/- 2 (SE) to 66 (16-116) ng/100 ml of AII from 16 +/- 4 to 52 +/- 13 pmol/liter and of [des-Asp1]AII from 2 +/- 0.7 to 12 +/- 4 nmol/liter. Incremental infusions of [des-Asp1]AII in the sodium replete state resulted in progressive increases in the plasma levels of aldosterone in all dogs. In comparison with a previous study in which dogs were infused with AII, it was apparent that [des-Asp1]AII was equally or slightly more potent in stimulating aldosterone and had a higher metabolic clearance rate than AII. [des-Asp1]AII stimulated aldosterone in four of the five sodium-depleted dogs but no steepening of the [des-Asp1]AII/aldosterone dose-response curves was apparent. These results do not support the hypothesis that circulating [des-Asp1]AII mediates the effect of AII on aldosterone in the dog.
Significance of renin and angiotensin in hypertension.
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Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine, and gentamicin.
Furosemide was shown to decrease inulin clearance in 20 of 27 normal subjects. The depression in inulin clearance occurred in both water-loaded and non-water-loaded subjects. The renal clearance of practolol, but not digoxin, was reduced when furosemide was given. The average total plasma clearances of gentamicin and of cephaloridine over a 6-hr period were decreased after furosemide. The reduced clearances of the antibiotics were associated with higher plasma levels, the increase in antibiotic concentration being as much as 100% at 1 hr after an intravenous bolus injection.
The effect of sodium deprivation and of angiotensin II infusion on the peripheral plasma concentrations of 18-hydroxycorticosterone, aldosterone and other corticosteroids in man.
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Effect of angiotensin-converting enzyme inhibitor (SQ 20881) on the plasma concentration of angiotensin I, angiotensin II, and arginine vasopressin in the dog during hemorrhagic shock.
The effect of an angiotensin-converting enzyme inhibitor on the circulating levels of angiotensin I, angiotensin II, and arginine vasopressin was studied in dogs subjected to hypotensive hemorrhagic shock. In dogs subjected to hemorrhage but not given the inhibitor, angiotensin II rose 20-fold (from 69 to 1,343 pg/ml of plasma), whereas in dogs subjected to hemorrhage but pretreated with the inhibitor, angiotensin II rose only 2-fold (from 92 to 171 pg/ml of plasma). In the pretreated dogs angiotensin I rose 30-fold (from 108 to 3,232 pg/ml of plasma). There was no statistically significant difference between the vasopressin levels found in the untreated dogs and the levels found in dogs given the inhibitor (1,016 and 1,095 pg/ml of plasma). Of the 15 dogs in the untreated group, five died before retransfusion was completed (four of cardiac failure and one of cardiac arrhythmia); none of the 10 dogs in the inhibitor-treated group died. These observations suggest that the very high levels of angiotensin II observed following severe hemorrhage do not contribute significantly to the increased secretion of vasopressin and that the inhibitor protects against death, possibly by suppressing the very high blood levels of angiotensin II observed following this type of experimental hemorrhagic shock.
The concentration of angiotensins I and II in blood from the pulmonary artery and left ventricle of man.
The concentrations of angiotensin I (AI) and II (AII) were determined by radioimmunoassay in blood from the main pulmonary artery (MPA) and left ventricule (LV) of ten subjects with rheumatic valvular heart disease. The levels of AI were consistently higher in MPA plasma (21.8+/-2.4 pmol/1) than in LV plasma (14.7+/-2.0 pmol/1), paired t, P less than 0.001. The levels of AII were consistently lower in MPA plasma (21.8+/-4.7 pmol/1) than in LV plasma (33.8+/-7.2 pmol/1), paired t, P less than 0.001. The AII antiserum cross-reacted with three metabolites of the hormone, [des-Asp1]angiotensin II, [des-(Asp1, Arg2)angiotensin II [des-(Asp1, Arg2 Val,3]angiotensin II. To characterize the nature of circulating AII immunoreactive material, paper chromatography was used to separate AII from its immunoreactive metabolites. The results showed that 84-100% of the AII immunoreactive material from both MPA and LV plasma chromatographed with the mobility of authentic angiotensin II. The mean pulmonary conversion of endogenous AI was 33+/-4.8% and the net extraction of AII by peripheral tissues was 33+/-4.1%.
The effect of angiotensin II infusion on plasma corticosteroid concentrations in normal man.
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Blood pressure and plasma angiotensin II concentration after renal artery constriction and angiotensin infusion in the dog. (5-Isoleucine)angiotensin II and its breakdown fragments in dog blood.
We measured arterial plasma angiotensin II concentration, renal blood flow, and arterial blood pressure in six conscious dogs during intravenous infusion of angiotensin II (5, 10, and 20 ng/kg per min). The same measurements were made on a different occasion in the same six animals, while they were conscious, before and during constriction of a main renal artery. Arterial blood pressure and plasma angiotensin II rose and renal blood flow decreased in both experiments. The similarity of regressions for plasma angiotensin II concentration and arterial blood pressure in the two experiments strongly suggests that the rise of circulating angiotensin II after renal artery constriction is sufficient to account for the hypertension by its direct pressor action. As discussed, a different mechanism seems likely to be involved in the later stages of renal hypertension. Angiotensin II is more likely to be in the 5-isoleucine form than in the 5-valine form in the dog. In contrast to the rat, plasma concentrations of the heptapeptide (angiotensin III), hexapeptide, and pentapeptide fragments of angiotensin II are low in the dog.
Angiotensin II and angiotensin III in rat blood.
Angiotensin II and its metabolites, [des-Asp-1]-angiotensin II (angiotensin III), [des-(Asp-1,Arg-2)]angiotensin II, and [des-(Asp-1,Arg-2,val-3)]angiotensin II, were measured in arterial and venous plasma from normal rats. Paper chromatography was used to separate the peptides which were measured with a radioimmunoassay method using an angiotensin II antiserum which had a 100% cross-reaction with each of these metabolites. A mean of 33% of the immunoreactive material in arterial plasma was angiotensin II, 58% angiotensin III, and 9% [des-(Asp-1,Arg-2)]angiotensin II/[des-(Asp-1,Arg-2,Val-3)]angiotensin II. A similar distribution was found in venous plasma. This and other evidence indicates that angiotensin-induced aldosterone secretion in the rat, unlike that in other mammalian species so far studied, may be mediated by angiotensin III.
Angiotensin II and its heptapeptide (2-8), hexapeptide (3-8), and pentapeptide (4-8) metabolites in arterial and venous blood of man.
We made separate measurements of angiotensin II (A II) and of its immunoreactive metabolites (2-8 heptapeptide, 3-8 hexapeptide, and 4-8 pentapeptide) in arterial and venous plasma from subjects with widely different plasma levels of the peptides. A II and its three metabolites were extracted from blood, separated by paper chromatography, and measured by radioimmunoassay using an A II antiserum which had a 100% cross-reaction with each metabolite. In contrast to results of previous studies, A II was found to predominate in both arterial (60-100%) and venous (55-100%) blood. The biologically active 2-8 heptapeptide metabolite accounted for only 10% of the activity in arterial plasma. Radioimmunoassay of venous plasma extracts using an A II antiserum which had a low cross-reaction with the 3-8 hexapeptide and the 4-8 pentapeptide confirmed the results obtained using the antiserum which had a 100% cross-reaction with the metabolites. We conclude that radioimmunoassay methods for measuring A II in venous blood may be more accurate and relevant than has previously been recognized. The small difference between A II concentrations in arterial and venous plasma suggests further that there may be significant conversion of angiotensin I (A I) to A II in the limb vasculature.
Renin, angiotensin II and III in acute renal failure: note on the measurement of of angiotensin II and III in rat blood.
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Role of bile acids in the pathogenesis of aspirin-induced gastric mucosal hemorrhage in rats.
The simultaneous oral administration of acetylsalicylic acid (64 mg per kg) and taurocholic acid (2.5 mM) to rats induced gastric hemorrhagic mucosal bleeding in 82.4% of animals compared with 29.7% of animals given acetylsalicylic acid alone. Taurodeoxycholic acid and glycocholic acid with acetylsalicylic acid also significantly increased the incidence of gastric hemorrhagic mucosal bleeding compared with the control animals, but cholic acid, chenodeoxycholic acid, and deoxycholic acid did not have a significant effect. Hemorrhagic mucosal lesions were not observed when the bile acids studied were administered alone. These results indicate a possible role for certain bile acids in the pathogenesis of gastric mucosal bleeding after the ingestion of aspirin.
The clinical value of renin and angiotensin estimations.
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Continuous intravenous infusion of small doses of insulin in treatment of diabetic ketoacidosis.
Continuous intravenous infusion of small amounts of insulin has been used in the management of a series of patients with diabetic ketoacidosis. In 13 patients with a plasma glucose level on admission of 725 mg/100 ml (+/- 80 S.E. of mean) and an arterial pH of 7.07 +/- 0.05 a mean loading dose of 6.5 +/- 0.82 units of soluble insulin was administered intravenously, and thereafter a sustaining infusion of 6.5 +/- 0.82 U/hr was continued until ketosis was corrected and the plasma glucose fell below 300 mg/100 ml. The total insulin dose needed to achieve this was 39.2 +/- 6.6 units given over a 3 to 10-hour period. Plasma insulin was measured in patients who had not previously received insulin and the mean level at an infusion rate of 4 U/hr was 75.6 +/- 8.0 muU/ml. Plasma glucose fell at a regular rate of 101 +/- 11 mg/100 ml/hr, and ketosis improved in parallel. Plasma potassium was well maintained throughout treatment. This regimen of treatment was clinically effective and simple to follow.
The effect of fasting and food on the rate of purine biosynthesis de novo in the rat spleen.
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