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Biomedical subjects

J E Sealey

Publications and source records attributed to J E Sealey.

At least 127 records · Page 7Linked to original sources
PubMed1981

Relationship between plasma renin and cortisol in hypertensive patients.

1. Plasma cortisol at 08.00 hours was significantly higher (P less than 0.005) in patients with high-renin essential or renovascular hypertension (22.6 +/- 1.6 microgram/100 ml) than in patients with normal-renin (15.4 +/- 1.2) or low-renin (11.9 +/- 1.2) forms of hypertension. 2. Plasma cortisol at 12.00 or 16.00 hours did not differ significantly among the three groups; thus the diurnal swing in plasma cortisol was steepest in patients with high plasma renin. 3. Among all patients studied, there was a direct relationship between 08.00 hours plasma cortisol and ambulatory plasma renin activity (r = 0.65, P less than 0.001). 4. In patients with high-renin values, 08.00 hours plasma cortisol fell by 39 +/- 6% after 10 days treatment with the converting enzyme inhibitor captopril. No consistent decreases were observed in the normal- or low-renin groups. 5. We conclude that the renin--angiotensin system may interact with the pituitary--adrenal axis to influence circulating levels of cortisol. This effect might conceivably contribute to the pathogenesis of certain high-renin states.

Circadian Rhythm↗
PubMed1981

Effect of captopril and aprotinin on inactive renin.

Inactive renin (prorenin) was measured in plasma from untreated hypertensive patients after acute (60 min) administration of the angiotensin I converting enzyme inhibitor captopril, after 4 weeks of treatment with captopril, and after an acute infusion of the protease inhibitor aprotinin. Inactive renin was unchanged during acute captopril therapy despite a 4-fold increase in active renin. In contrast, after 4 weeks of treatment with captopril, inactive renin had increased 2-fold and active renin was also elevated, but to a greater degree (6-fold). Active renin was significantly suppressed by the aprotinin infusion, to about 25%, but the inactive plasma renin level was apparently unchanged. These studies demonstrate that the time course of the responses of active and inactive plasma renins are different; the inactive renin level seems to change more slowly than does active renin in response to the same stimulus. The results also show that a neutral serine protease inhibitor can rapidly reduce the circulating level of active renin. This observation is consistent with the possibility, but does not prove it, that a kallikrein-like enzyme normally activating prorenin was inhibited by aprotinin.

Aprotinin↗
PubMed1981

Contact activation of human plasma prorenin in vitro.

Acid activation of plasma prorenin occurs during dialysis to pH 3.3. and also during subsequent dialysis to pH 7.4. The latter, alkaline phase, involves Hageman factor-dependent formation of kallikrein, which in turn activates prorenin. The present study evaluates whether prorenin activation always occurs whenever kallikrein is activated in plasma. TAME esterase activity was used as a measure of plasma kallikrein activity an increase was observed during the alkaline phase of acid activation of prorenin. TAME esterase activity was absent when Hageman factor- or prekallikrein-deficient plasmas were similarly assayed and prorenin was not activated. Kaolin treatment of normal plasma rapidly increased TAME esterase activity at both 25 degrees and -4 degrees C, but no prorenin activation occurred. Similar changes in TAME esterase activity were observed in acid-treated plasma, in which setting prorenin was activated. No change in TAME esterase or renin activity occurred after addition of kaolin to acid-treated plasma deficient in Hageman factor; however, both enzymatic activities increased slightly in acidified prekallikrein-deficient plasma. Mixtures of these deficient plasmas exhibited normal kaolin activation of both TAME esterase and prorenin after acidification. Thus both Hageman factor and prekallikrein are needed for optimal contact activation of prorenin. These results demonstrate that prorenin activation does not always occur when active kallikrein is present in plasma. Prior acidification appears to be a prerequisite. Acidified prorenin may be more susceptible to cleavage; alternatively, competing substrates and/or inhibitors of kallikrein may be destroyed at acid pH, thereby permitting kallikrein to activate prorenin. Under normal conditions, activation of the plasma kallikrein-kinin system appears unlikely to result in activation of prorenin in vivo.

Dialysis↗
PubMed1981

The intrinsic coagulation-kinin pathway, complement cascades, plasma renin-angiotensin system, and their interrelationships.

Activation of the classical complement pathway is initiated by immune complexes consisting of IgM antibody or IgG subclasses 1, 2, and 3. Binding to Clq leads to activation of C1s and digestion of C4 and C2 to yield a C3 convertase. The alternative complement pathway is initiated by complex polysaccharides as well as immune complexes of the IgA class which interact with Factors B, D, C3, and properdin to yield a stabilized C3 convertase consisting of PC3Bb. Cleavage of C3 and C5 by either pathway yields the C3a and C5a anaphylatoxins which cause histamine release from mast cells and formation of the C5b6789 attack complex causes cell lysis. Both immunologic and nonimmunologic tissue damage can initiate the surface dependent pathways of coagulation, fibrinolysis, and kinin formation. Surface bound Hageman Factor interacts with complexes of prekallikrein and HMW-kininogen as well as Factor XI and HMW-kininogen to form activated Hageman factor, kallikrein, and Factor XIa. Factor XIa continues the coagulation pathway, kallikrein and Factor XIa convert plasminogen to plasmin and kallikrein digests HMW-kininogen to yield bradykinin. The Cl inhibitor, which inactivates Cls is the major plasma inhibitor of activated Hageman factor and kallikrein. In its absence, a potentially fatal form of angioedema is seen. The inactivator of the C3a and C5a anaphylatoxins is identical to carboxypeptidase N, the major plasma inactivator of bradykinin thus demonstrating the common control mechanisms which regulate the complement and kinin-forming pathways.

Blood Coagulation↗
PubMed1980

An inactive, prorenin-like substance in human kidney and plasma.

1. Plasma prorenin (inactive renin), which accounts for about 70% of the total renin in human plasma, was almost completely separated from active renin by affinity chromatography on Cibacron blue F3G-A-agarose. The slight residual renin activity present in the prorenin peak can be removed on concanavalin A-Sepharose, demonstrating that prorenin is completely inactive. 2. The renin activity of both human renal cortical extract and renal perfusate increased after incubation with trypsin. This trypsin-activable renin accounted for 15 and 40% of the total renin in extract and perfusate respectively. 3. Trypsin-activable renin from both renal extract and renal perfusate was, like plasma prorenin, almost completely separated from active renin on Cibacron blue F3G-A-agarose. After additional chromatographic steps, the trypsin-activable renin from renal cortical extract was found to be completely inactive. 4. We conclude that human kidney contains, and is able to release, a trypsin-activable renin that resembles plasma prorenin. It may differ from many of the 60 000 molecular-weight forms of renin previously identified in renal extracts, since these possess considerable intrinsic renin activity and probably represent a complex of renin with a binding protein.

Angiotensin I↗
PubMed1979

Plasmin can activate plasma prorenin but is not required for the alkaline phase of acid activation.

1. Plasma prorenin is an inactive form of renin that is converted into active renin at alkaline pH in previously acidified plasma; this conversion of prorenin into renin is mediated by Hageman factor-dependent activation of prekallikrein, which, in turn, leads to prorenin activation. 2. Since plasma kallikrein can activate plasminogen, the present studies were designed to evaluate whether alkaline-phase activation of prorenin by plasma kallikrein is mediated via plasminogen activation. 3. We demonstrated that plaminogen is present in acid-treated plasma in sufficient quantity to convert prorenin into renin after activation by streptokinase. 4. However, alkaline-phase activation was completely normal in plasminogen-free plasma. 5. Therefore alkaline-phase activation of plasma prorenin is mediated by plasma kallikrein but is not dependent on kallikrein activation of plasminogen.

Enzyme Activation↗
PubMed1979

Initiation of plasma prorenin activation by Hageman factor-dependent conversion of plasma prekallikrein to kallikrein.

Plasma prorenin is an inactive form of renin (EC 3.4.99.19) that can be converted to active renin in acid-treated plasma by an endogenous serine protease that is active at alkaline pH (alkaline phase activation). To identify this enzyme we first tested the ability of Hageman factor fragments, plasma kallikrein (EC 3.4.21.8), and plasmin (EC 3.4.21.7) to activate prorenin in acid-treated plasma. All three enzymes initiated prorenin activation; 50% activation was achieved with Hageman factor fragments at 1 microgram/ml, plasma kallikrein at 2-4 microgram/ml, or plasmin at 5-10 microgram/ml. We then showed that the alkaline phase of acid activation occurred normally in plasminogen-free plasma but was almost completely absent in plasmas deficient in either Hageman factor or prekallikrein; alkaline phase activation was restored to these latter plasmas when equal parts were mixed together. Therefore, both Hageman factor and prekallikrein were required for alkaline phase activation to occur. We then found that, although plasma kallikrein could activate prorenin in plasma deficient in either Hageman factor or prekallikrein, Hageman factor fragments were unable to activate prorenin in prekallikrein-deficient plasma. These studies demonstrate that alkaline phase prorenin activation is initiated by Hageman factor-dependent conversion of prekallikrein to kallikrein which, in turn, leads to activation of prorenin. In this fashion, we have revealed a possible link between the coagulation-kinin pathway and the renin-angiotensin system.

Angiotensin I↗
PubMed1979

The immediate pressor response to saralasin in man: a test of angiotensin II receptor vacancy.

Saralasin, 10 microgram/kg per min, caused an immediate rise in blood pressure in 52 of 57 (91.2%) hypertensive patients. The increase in diastolic pressure averaged 18.8 +/- 1.83 mm Hg (mean +/- SE) in normal renin patients on a normal salt intake. This immediate pressor response was absent in only five high renin patients and, conversely, was very large in three low renin patients. Direct arterial recordings are necessary to define the response accurately; it begins in 60--90 seconds, peaks in amplitude at 2.05 +/- 0.38 minutes, and subsides over the next 5 minutes in normal renin and high renin patients. The blood pressure elevation is inversely related to background plasma renin activity (r = -0.66, P less than 0.001), and also is directly, but weakly, related to 24-hour urinary sodium excretion (r = + 0.29). Therefore, the amplitude of the elevation is predictably diminished by the rise in plasma renin consequent to prior sodium restriction, and also by preliminary receptor exposure to low dose nonpressor infusions of saralasin itself (0.01-0.1 microgram/kg per min). Phentolamine had no effect on the response in two patients. We propose that the immediate pressor response to saralasin is related directly to the preexisting degree of vacancy of angiotensin II vascular receptors and that the initial agonistic action of the drug may prove useful in defining the angiotensin II receptor status in hypertensive diseases.

Angiotensin II↗
PubMed1979

Nephrotic syndrome: vasoconstriction and hypervolemic types indicated by renin-sodium profiling.

Studies of 16 adults with nephrotic edema reveal a spectrum of disease, the extremes of which suggest two different pathophysiologic forms. Patients with the "classic" form--vasoconstriction or hypovolemic nephrosis--have high renin and aldosterone levels that are stimulated rather than suppressed by salt-loading but become lower before steroid diuresis. These patients have minimal lesion disease and, perhaps from diffuse capillary damage, tend to have hypovolemia with renin-induced vasoconstriction. Patients with the second, and heretofore undescribed, form--hypervolemic or overfilling nephrosis--have low renin and aldosterone values that rise normally after sodium depletion. Hypertension, mild renal insufficiency, hypervolemia, and steroid resistance with chronic glomerulonephritis are seen histologically. This form appears volume overloaded from impaired renal sodium excretion. In remission of either type, renin system deviations tend towards normal, but one form does not convert to the other. Renin-sodium profiling may help reveal the two forms and predict steroid responsiveness.

Adolescent↗
PubMed1978

Activation of inactive plasma renin: evidence that both cryoactivation and acid-activation work by liberating a neutral serine protease from endogenous inhibitors.

1. We have found that 'acid'-activation of inactive human plasma renin is a two-phase process. About 30% of activation occurs during dialysis to pH 3.3; the remaining 70% occurs at alkaline pH. 2. The 'alkaline phase' of activation has a pH optimum between 7.5 and 8.4. It is inhibited by unacidified plasma and by soya-bean or lima-bean trypsin inhibitors. 3. 'Cryoactivation' of inactive plasma renin, which occurs at -4 degrees C and alkaline pH, is also inhibited by soya-bean or lima-bean trypsin inhibitors and by the serine protease inhibitors diisopropylphosphorofluoridate and benzamidine. 4. Thus endogenous neutral serine proteases participate in the activation of inactive plasma renin in vitro. Their action is prevented in the circulation by inhibitors which are inactivated by acid or cold.

Cold Temperature↗
PubMed1978

Effects of indomethacin alone and during diuretic or beta-adrenoreceptor-blockade therapy on blood pressure and the renin system in essential hypertension.

1. Indomethacin was administered alone or in addition to either diuretic or propranolol therapy to three groups of patients with essential hypertension on a free sodium diet. 2. Indomethacin administration reduced renin secretion by about 30% in untreated uncomplicated hypertensive patients and by about 75% in those whose renin secretion had either been stimulated or suppressed by maintained diuretic or beta-adrenoreceptor-blockade therapy. 3. Indomethacin administration produced no net effect on blood pressure in untreated patients with uncomplicated hypertension but it blunted or reversed the antihypertensive effect of either diuretic or propranolol therapy. 4. Salt and water retention may be an important factor in the blood pressure-raising effect of indomethacin during diuretic or propranolol therapy: In addition, prostaglandin synthesis may be important in counteracting increased alpha-adrenergic tone, which may limit the blood pressure-lowering effect of beta-adrenoreceptor-blockade. 5. Because of these interactions and their pressor potential indomethacin should be used with caution when combined with either diuretics or beta-adrenoreceptor blockers.

Adult↗