A commentary on the measurement of renin and angiotensin.
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Angiotensin II↗
Biomedical subjects
F M Bumpus
Publications and source records attributed to F M Bumpus.
Measurement of renin activity in human plasma.
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Angiotensin II↗
Role of renin-angiotensin system in chronic renal hypertensive rats.
The role of renin-angiotensin system has been examined in the maintenance of hypertension in acute and chronic two-kidney (36 weeks) and chronic one-kidney (12 weeks) Goldblatt hypertensive rats using three inhibitors of this system. The inhibitors used were URI-73A, a synthetic analog of lysophosphatidylethanolamine, which inhibits renin both in vivo and in vitro, SQ14,225, a potent converting enzyme inhibitor, and [Sar1, Thr8] angiotensin II, an angiotensin II antagonist. When the inhibitors were administered in acute (high renin) hypertensive rats, they all lowered blood pressure significantly. However, in the chronic (low renin) hypertensive phase, both renin and converting enzyme inhibitors lowered blood pressure, whereas, Sar1, Thr8 failed to lower blood pressure. The renin inhibitor lowered plasma renin activity (PRA), and SQ14,225 and [Sar1, Thr8] Ang II increased PRA. Further studies on water and electrolyte balance with one-kidney model hypertensive and uninephrectomized control rats showed no change in plasma volume. However, there was increased 24-hour urinary output and increased sodium excretion. This study indicates that in chronic renal hypertensive rats, blood pressure reduction is possible by either renin on converting enzyme inhibitor, but not by angiotensin antagonists. Since volume did not change either during the development or reversal of hypertension, volume did not appear to play a major role in the maintenance of hypertension.
Angiotensin II↗
Effect of converting enzyme inhibitor (SQ14,225) on myocardial hypertrophy in spontaneously hypertensive rats.
The potent converting enzyme inhibitor (CEI) SQ14,225, which is known to prevent the formation of angiotensin II (AII) has been used to evaluate the role of AII in the development and reversal of cardiac hypertrophy. The present study describes the effect of CEI on blood pressure (BP) and myocardial hypertrophy (prevention and reversal) in the spontaneously hypertensive rat (SHR). A group of 3-week- and 8-week-old male SHR was treated with CEI (30 mg/kg in drinking water) for 6 weeks. An additional group of SHR was also treated with a combination of CEI and a diuretic (hydrochlorothiazide, 500 mg/liter). Heart weight, BP, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), hydroxyproline, myocardial catecholamines, and plasma renin activity (PRA) were determined. In the prevention study, we found a significant reduction in the ratio of heart weight to body weight along with the prevention of hypertension (200 vs 145 mm Hg, p less than 0.001). Similar reductions in BP and heart weights were obtained with the reversal group. A better BP control was noted in the CEI and hydrochlorothiazide group. The reduction of heart weight was associated with a reduction in RNA and hydroxyproline content. In all groups, we found a significant increase in PRA (p less than 0.001) and a slight increase in tissue catecholamine concentration. No change in kidney weight was found in any group. Data clearly showed that oral administration of CEI prevented and reversed cardiac hypertrophy in SHR. Reversal was associated with a decrease in myocardial collagen content. These data indicate that prevention of AII formation in combination with BP control can prevent and reverse cardiac hypertrophy in SHR. Of course, whether or not CEI acts only through the renin angiotension system is still speculative.
Animals↗
Effects of SQ 20,881 on the intact kidney of dogs with two-kidney, one clip hypertension.
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Angiotensin II↗
Isolation of aldosterone-stimulating factor (ASF) and its effect on rat adrenal glomerulosa cells in vitro.
A protein fraction has been isolated from normal human urine which upon chronic administration produced hypertension in rats. The hypertension is associated with retention of sodium and increased circulating aldosterone. The protein fraction has been purified to homogeneity, and its molecular weight has been determined to be 26,134 daltons by equilibrium ultracentrifugation. The compound has been identified to be clearly different from ACTH, angiotensin II, and beta-lipotropin. It stimulated aldosterone production from rat glomerulosa cells in vitro in a dose-dependent fashion from 10(-9) to 10(-4)M with a maximum stimulation at 10(-7) where a fourfold increase was obtained during 2 hours of incubation. Removal of some carbohydrate moieties by insoluble neuraminidase caused a twofold increase in aldosterone production in vitro. The protein fraction has been named "aldosterone-stimulating factor" or "ASF." Further studies are in progress to define its physiological role.
Adrenal Cortex↗
Steroidogenic characteristics of a new aldosterone-stimulating factor (ASF) isolated from normal human urine.
The steroidogenic properties of a glycoprotein fraction (urinary ASF), isolated from normal human urine, were studied in collagenase-dispersed rabbit adrenal capsular cells in 1) define the requirements for its steroidogenic activity, and 2) assess its site and mode of action. When incubated with adrenal cell suspension at 37 degrees C for 2 hours, urinary ASF induced dose-related increases in both aldosterone and corticosterone production. However, urinary ASF was less potent (ED50 = 10(-9) M) than either angiotensin II (ED50 = 8 x 10(-11) M) or ACTH (ED50 = 4 x 10(-11) M). Increases in cyclic AMP accompanized the steroidogenic response to ACTH but not to either urinary ASF or AII. Deprivation of potassium in incubation media or the addition of ouabain (1 mM) during incubation completely inhibited the steroidogenic response to either urinary ASF, ACTH, or AII. Like ACTH and AII, urinary ASF increased conversion of corticosterone to aldosterone. Specific competitive antagonist of AII (Sar1, Thr8, AII) and ACTH ([I1e9]ACTH1-24) did not prevent the ASF-induced increase in aldosterone production. These results suggest that urinary ASF is readily distinguishable from ACTH. Although it shares similar steroidogenic properties with AII, the inability of AII antagonist to block its effects suggests that it acts at a separate receptor site.
Adenosine Triphosphatases↗
Localization, purification, and biological activity of a new aldosterone-stimulating factor.
An aldosterone-stimulating factor (ASF) has been isolated from normal human urine and found to be a glycoprotein with a molecular weight of 26,000 daltons. ASF stimulated aldosterone production both in vivo and in vitro. ASF was found to be different from other known aldosterone secretogogues by the use of high performance liquid chromatography (HPLC). The retention time of ASF was different (17.0 minutes) from ACTH (retention time, 28.4 minutes), beta-lipotropin (retention time, 20.5 minutes), and angiotensin II. Proteolytic enzyme digestion and purification of ASF by HPLC yielded a smaller molecule (retention time, 22.0 minutes) with a molecular weight of 4000 daltons. This smaller molecule also stimulated aldosterone production in vitro. This showed that the structural requirement for steroidogenesis may be residing in a smaller molecule. ASF failed to produce hypertension in adrenalectomized rats. By immunofluorescence (using fluorescein conjugated antibodies), ASF was found to be localized in the anterior lobe of the pituitary gland. Data suggest that ASF, a new aldosterone-stimulating hormone that has not been described before, is secreted by the pituitary gland, and the adrenal gland appears to be the target organ for the biological activities.
Adrenalectomy↗
Development and preliminary application of a new assay for aldosterone stimulating factor.
A new assay method has been developed to measure aldosterone stimulating factor (ASF) quantitatively. This method utilizes a combination of affinity chromatography and high pressure liquid chromatography (HPLC). Antibodies raised against ASF, coupled to Affi-Gel 10, were used as the affinity column, and adsorbed ASF was eluted with 4 M urea. Quantitation was based on the external standard method of analysis using the area of the standards as controls, which were previously tested by HPLC for purity. The amount of ASF in the unknown samples was calculated on the basis of the area of the peak emerging at the retention time of ASF. A parallel bioassay using adrenal glomerulosa cells was also done to assess the biological activity. In eight normal volunteers, the urinary ASF was 146 +/- 4.6 ng/24 hr urine, whereas in plasma it was 70.5 +/- 6.5 ng/100 ml. The method is reproducible, specific for ASF, and showed less than 3% inter- or intraassay variability. In a preliminary study, when ASF was quantified from the 24-hour urine of two patients with adrenal hyperplasia, a significantly higher level of ASF was found (750 and 1020 ng/24 hr urine). These data suggest that ASF may be of pathological significance in certain hypertensive patients, especially in the hypertension associated with hyperaldosteronism.
Adrenal Glands↗
Effects of frog-skin angiotensin II in amphibians.
The role of frog-skin angiotensin II (AII) in amphibia was studied by comparing the sodium and water permeability effects of three angiotensins (AII): frog skin (Ala-Pro-Gly-[Ile3, Val5]-Ang II), human [( Asp1, Ile5]-AII), and Japanese goosefish [( Asn1-Val5]-AII). Frog-skin AII increased the short-circuit current (SCC) significantly after it was added to the dermal side of the isolated skin of the South American frogs, Leptodactylus chaquensis and ocellatus, and the toad, Bufo arenarum, in concentrations of 10(-6) M. In frogs, the effect was significant at 15 minutes and reached 45% over control after 2 1/2 hours. The effect cannot be achieved with concentrations lower than 10(-7) M. Since amiloride (10(-4) M) blocked the SCC response, and absence of chloride in the bathing fluid did not, the effect is probably dependent on sodium transport. Human AII (10(-6) M) produced a similar response in summer frogs that had been treated with 0.1% NaCl for 14 days. Goosefish AII was ineffective at similar concentrations, and none of the angiotensins modified SCC in the toad bladder. Hydrosmotic effects could be achieved with the three angiotensins, the response being dependent on seasonal and species factors but always considerably lower than that of the neurohypophyseal peptides. Vascular reactivity of the isolated frog hindlimbs was compared by dose-response curves. Potency ratios on a molar basis against frog-skin AII was 1.136 for human AII and 1.193 for goosefish AII. The results show that the effects of the angiotensins differ in both the response of SCC to frog-skin angiotensin and its higher vascular effects.
Amphibians↗
Synthesis of nonmammalian angiotensins and their comparative pressor properties in dogfish shark, domestic chicken, and rat.
To understand how vertebrates utilize angiotensins during evolutionary development, we undertook studies to synthesize and/or characterize angiotensin-like peptides from nonmammalian species. The present paper describes the synthesis of [Asp1,Val5,Asn9] angiotensin I (bull frog, Rana catesbeiana) (I), [Asn1,Val5,His9] angiotensin I (Japanese goosefish, Lophius litulon) (II), [Asn1, Val5,Asn9] angiotensin I (chum salmon, Oncorhynchus keta) (III), and [Asn1, Val5,Tyr9] angiotensin I (related to native angiotensin in snake, Elaphe climocophora (IV). Pressor properties of these peptides were compared with the peptides isolated from other species and related synthetic analogs in one representative species from three distinct classes of vertebrates: 1) elasmobranchs: spiny dogfish shark; 2) birds: domestic chicken; and 3) mammals: rat. The effect of angiotensins on short circuit current (to compare sodium and water permeability) was studied by adding these on the dermal side of the isolated frog skin. In the rat pressor bioassays, the above peptides possessed, respectively, I, 87.8%; II, 51.5%; III, 65.2%; and IV, 60.3% pressor activity of [Ile5] angiotensin II, which was blocked with a converting-enzyme inhibitor, captopril. In the conscious dogfish shark, the percentage increase of blood pressure based on preinjection level (= 100) in the dorsal aortic pressure was 35% to 60% for [Asp1,Ile5,His9] angiotensin I (human) (3 micrograms/kg), [Asp1,Val5,Ser9] angiotensin I (chicken) (3 micrograms/kg), [Asp1,Ile5] angiotensin II (3.6 micrograms/kg), and [Asn1,Val5] angiotensin II (6 micrograms/kg). Likewise, a 30% to 35% increase in blood pressure was obtained with angiotensin III (3 micrograms/kg), [Ile8] angiotensin II (4.4 micrograms/kg), and [Sar1,Ile8] angiotensin II (9.1 micrograms/kg). [Sar1,Thr8] angiotensin II and [Ile8] angiotensin I did not produce a significant pressor response even at high dose-level (8 micrograms/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin I↗