Angiotensin blockade by saralasin bolus injection.
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Biomedical subjects
Publications and source records attributed to M H Maxwell.
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The fine structure of the granules of circulating eosinophil leucocytes was studied in five adult black-necked crowned cranes. The interna within these granules showed various crystalline arrangements. Optical diffraction patterns of the crystals revealed linear arrangements measuring 6.2 and 3.8 nm and often, when these arrangements were superimposed, a hexagonal pattern was observed. Bundles of microfilaments measuring 5-7 nm in diameter were found frequently in crystal-containing granules. Staining with phosphotungstic acid (PTA) and various other cytochemical procedures gave results similar to those obtained previously in the shag and the duck. The PTA stain and peroxidase reaction product were found only in the externum of the granules whereas the acid hydrolases, acid phosphatase and arylsulphatase were located within the crystalline matrix and in or between the microfilaments. As with shag eosinophil granules, those of the crane did not appear to contain histone arginine and in this respect they differed from those of the duck and the fowl.
The responsiveness of plasma aldosterone levels to various stimuli was evaluated in 44 normal subjects, 17 patients with mild to moderate renal failure, 30 patients with terminal renal failure, and 13 anephric subjects. Plasma aldosterone, renin activity (PRA), cortisol, sodium, and potassium levels were measured before and after one hour of upright posture (N = 191); ACTH infusions (N = 76); and angiotensin II infusion (N = 36). Plasma aldosterone responses correlated (r greater than or equal to 0.53; p less than 0.02) with basal plasma aldosterone levels during upright posture in all four groups, with ACTH infusion in all groups except anephric subjects, and with angiotensin II administration in patients with mild to moderate renal failure or patients combined. These relationships were consistently closer than those between aldosterone responses and changes in PRA or basal PRA. However, postural aldosterone responsiveness at any given basal aldosterone level was significantly lower in patients with renal disease than in normal subjects, and this was associated with a parallel impairment in renin responsiveness. In contrast, when related to basal levels aldosterone responsiveness to ACTH or angiotensin II appreared to be comparable in normal subjects and patients with renal disease. Aldosterone responses to posture, ACTH, or angiotensin II did not correlate with associated changes in plasma cortisol, sodium, or potassium levels. These data suggest that basal adrenal secretory activity is a major factor conditioning aldosterone responsiveness to various stimuli in normal subjects as well as in patients with renal disease.
Enzyme cytochemical studies have been carried out on eosinophils in the fowl and the duck. Peroxidase was found in all regions of the Golgi apparatus, the rough endoplasmic reticulum and the perinuclear cisternae of the early cells. In fowl eosinophil granules irregular deposits of peroxidase and arylsulphatase final reaction product were found, but the acid phosphatase deposits were even. In the duck in contrast, peroxidase was demonstrated in the external part of the granule only. Acid phosphatase and arylsulphatase were found in both the interna and the externa of the duck eosinophil granules. An ammoniacal silver nitrate reaction for the presence of the histone arginine was also studied. Silver deposits were found occupying all regions of the granules of eosinophils from both species of bird. The presence of the hydrolytic enzymes acid phosphatase and arylsulphatase in avian eosinophil granules supports the theory that these structures are lysosomal in nature and that they correspond with mammalian eosinophils in this respect.
The ultrastructure of eosinophil granules from various aquatic and terrestrial birds has been described. Granules of three basic types were found. The first had a crystalline internum and was found only in the order Anseriformes, which included the black-necked screamer, ducks, geese and swans. The crystals occurred in three morphological forms. The second and least common granule examined contained a non-crystalline internum which was either homogeneous or composed of microfilaments or microtubules. The largest and most common group of birds had a homogenous granule with no internum shown. Homogeneous granules occurred less frequently than did those with interna.
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Ultrathin epoxy sections are commonly used in electron microscopy. More useful information can often be obtained by examining thicker 0.5--3.0 micron) resin sections under the light microscope. However, there are some histological stains that are unable to penetrate these resins. This short note describes the easy and rapid preparation of two resin-removal solutions which allow subsequent staining of 1.0 micron thick sections without obvious tissue damage and with excellent results using standard histological dyes.
A 10 mg bolus of the angiotensin blocker saralasin was injected 113 times in 68 subjects with essential or renovascular hypertension. Ninety percent of injections caused a transient increase in blood pressure, which correlated with plasma renin activity (PRA) (r = -0.54); Mean increase at 2 minutes was 21/13.4 mm Hg (P less than 0.001) and was independent of pre-injection control blood pressure, with a rapid decrease to or below control values thereafter. Thirty-seven subjects were studied on successive days before and after furosemide-induced sodium depletion (152 +/- 26 mEq [SE] sodium loss). In the low renin group, sodium depletion did not change PRA or the magnitude of the pressor response to saralasin, but significantly decreased control MAP by 13 mm Hg (P less than 0.01). In normal and high renin patients, MAP was unchanged after diuresis, but PRA increased significantly and the pressor response was attenuated. The net effect of sodium depletion was to reduce the pressor response to saralasin in all renin subgroups by 9 to 12 mm Hg. Saralasin bolus injection, unlike infusion, saturates available vascular receptors only briefly, eliminating prolonged pressor responses.
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A sorbent regenerative dialysate system for peritoneal dialysis has been developed (Pericycle). Clinical results and data demonstrate that the sorbent system provides a suitable dialysate. The sorbents effectively remove uraemic metabolites from the dialysate. Calcium and magnesium removed by the cartridge and glucose metabolised by the patient are replaced by the infusion system. The machine pumps regenerated dialysate into and spent dialysate out of the patients. A pressure sensor in the patient line prevents excessive inflow and outflow pressures by stopping the inflow or outflow pump respectively. The Pericycle provides a simple, safe, portable method for conducting peritoneal dialysis in the home or hospital.
The eosinophils present in the bone marrow of the fowl and the duck were classified into various maturational stages according to the shape of their nuclei and the content of their cytoplasm. The granules appeared to develop from dilations located at the extremities of the cisternae of the Golgi apparatus, whence they broke free, forming vesicles. By condensation they progressed from a flocculent type of granule to the definitive spherical homogeneous primary granule. Various staining techniques were applied in this study and it was found that, as in mammals, granules of two distinct types were present in developing avian eosinophils, and that they matured by transition from a primary granule to a specific stage.
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The prognostic value of renal vein and peripheral renin levels was analyzed in 66 patients with unilateral renal artery stenosis who underwent corrective surgery. Patient selection for operation was independent of renin results. Fifty-three percent of those with confirmed renovascular hypertension had renal vein renin ratios less than 2.0, ie, within the 95% confidence limit for the control group of 82 patients with essential hypertension. Thirty-four patients with clearly lateralizing renin data (ipsilateral:contralateral greater than or equal to 1.5 and contralateral:peripheral less than or equal to 1.3) were benefited by operation, but 23 additional patients with nonlateralizing data also benefited. No proposed scheme for renin data analysis detected more than 75% of those with renovascular hypertension. Although lateralizing renin data are highly predictive of operative benefit, nonlateralizing data do not necessarily herald operative failure and should not be dogmatically used to exclude surgical intervention.
Hypertensive crises were reported in three patients with hypertension associated with underlying renovascular occlusive disease during reduction of antihypertensive therapy. In each case, rebound hypertension was observed during clonidine hydrochloride withdrawal. Therapy with propranolol hydrochloride and diuretics had also been discontinued in two of the three patients. This and other reports of rebound hypertension during clonidine withdrawal are contrasted with the absence of reports of this syndrome in the setting of cessation of beta-adrenergic blockade therapy. This suggests that the discontinuation of clonidine therapy was primarily responsible for the hypertensive crises herein described. It is further concluded that rebound hypertension may follow gradual as well as abrupt reduction of clonidine dosage, and that patients with renovascular hypertension may be at greatest risk.
Abnormal urographic features were present in 60.7% of 250 patients with bilateral diseases. The urogram was relatively insensitive in the minority of patients whose lesions were of approximately equivalent severity bilaterally. In bilateral renovascular disease, the urogram demonstrated some surgical prognostic value that was not evident in unilateral renovascular disease. Furthermore, in patients with bilateral disease, the urogram was helpful in deciding between unilateral or bilateral operation.
In two hypertensive patients with renal-artery stenosis, overactivity of the renin-angiotensin system was ruled out by investigations of renin and aldosterone concentrations and by the lack of a vasodepressor response to angiotensin blockade with saralasin. Nevertheless, hypertension was cured by renal revascularisation. The date suggest that there is a form of renovascular hypertension which is not mediated by the renin-angiotensin system.
Saralasin, a specific competitive inhibitor of angiotensin II, was administered in a controlled, prospective study designed to test the hypothesis that this agent is a useful tool for the detection of renovascular hypertension. 13 patients, 11 with renovascular hypertension and 2 with high-renin essential hypertension, showed a gross, readily apparent decrease in blood pressure after receiving saralasin. 8 patients with essential hypertension and normal or low renin levels exhibited no depressor response to the drug. In the patients with renovascular hypertension, blood pressure response during angiotensin blockade compared favourably with renal vein renin determinations as a predictor of operative results. Because saralasin testing has resulted in few if any falsely positive or negative results when considered as a diagnostic procedure for renin-mediated hypertension, and because it is safe, it may become an ideal initial screening procedure. The saralasin test (either bolus injection or sustained infusion) is completely valid only if the patient is mildly salt-depleted, is not taking other antihypertensive medication, and is genuinely hypertensive at the time of the test.