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Biomedical subjects

S A Atlas

Publications and source records attributed to S A Atlas.

At least 109 records · Page 6Linked to original sources
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

Reactive hyper-reninaemia to angiotensin blockade identifies renovascular hypertension.

1. Saralasin and converting enzyme inhibitors SQ 20881 and captopril induced increases in plasma renin activity to greater than 14 ng h-1 ml-1 in 43 out of 44 patients with untreated renovascular hypertension when studied in the seated position and on normal sodium intake. This degree of response was absent in patients with normal-renin essential hypertension and present in only three out of 26 with high-renin essential hypertension. 2. Reductions of greater than approximately 9% in diastolic pressure in response to these three drugs occurred regularly in renovascular hypertension (95%) but also frequently in high-renin (65%) and normal-renin (26%) essential hypertension. 3. Prior sodium depletion abolished the specificity of the renin and depressor responses to angiotensin blockage for renovascular hypertension. 4. Some patients with bilateral renovascular and all with malignant hypertension also exhibited these responses to angiotensin blockade that are characteristic of unilateral renovascular hypertension.

Angiotensin II↗
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

Developmental pharmacology and the Ah locus: regulatory and temporal genes affecting teratogenesis.

The "Ah cluster" is a group of regulatory, temporal, and structural genes associated with the inducibility of numerous monooxygenase activities by polycyclic aromatic compounds such as 3-methylcholanthrene. Age- and tissue-specific differences in temporal control of these enzymes are shown to exist. These differences could be important in the age- and tissue-specific differences in one's susceptibility to cancer, drug toxicity, and birth defects. Allelic differences at the Ah locus are shown in the mouse to be associated with benzo[a]-pyrene-produced in utero toxicity: increased stillborns, resorptions, and dysmorphogenesis, plus decreased fetal weight.

9,10-Dimethyl-1,2-benzanthracene↗
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

Carcinogenic benzo(a)pyrene metabolites bound to DNA: metabolic formation by human cultured lymphocytes and by human liver microsomes.

Sonicates of human cultured lymphocytes metabolize (benzo(a)pyrene to at least two intermediates that bind covalently to deproteinized DNA in vitro. The major peak represents the 4,5-oxide bound to nucleoside(s). No correlation is found between 'aryl hydrocarbon hydroxylase activity' (or its inducibility) and benzo(a)pyrene metabolites generated by human lymphocytes and bound to DNA in vitro. Human liver microsomes produce in vitro at least six such reactive intermediates which, bound to deproteinized DNA nucleosides, are separable by chromatography. The major peak represents the 7,8-diol-9,10-epoxides bound to nucleoside(s): this highly reactive intermediate is believed to be one of the ultimate carcinogenic forms of benzo(a)pyrene.

Aryl Hydrocarbon Hydroxylases↗
PubMed1977

Plasma renin and "prorenin" in essential hypertension during sodium depletion, beta-blockade, and reduced arterial pressure.

An inactive form of renin is activated by incubating human plasma at -5 degrees C. The relative proportions of active renin and this cryoactivatable "prorenin" in plasmas of untreated hypertensive patients varied widely. However, prorenin increased in parallel with active renin after sodium deprivation or diuretic therapy in 36 patients; the increases were similar whether or not blood-pressure fell. In contrast, propranolol administration in 22 patients lowered active renin in all, but it increased prorenin by 98% in 15 in whom systolic pressure fell. In the other 7 blood-pressure did not change, and beta-blockade produced a fall in total renin (active renin plus prorenin) while prorenin was unchanged. For all 22 there was an inverse relationship between propranolol-induced changes in plasma-prorenin and systolic pressure (r=-0-77, P less than 0-001). The fraction of active plasma-renin fell during propranolol administration from 43% to 18%, regardless of the blood-pressure response. Clonidine produced similar changes in 10 patients. Thus, sodium depletion stimulates total renin release, while propranolol and clonidine produce divergent responses of active renin and prorenin, the changes in prorenin depending on the changes induced in blood-pressure. These observations suggest that propranolol may block intrarenal conversion of prorenin to active renin while also suppressing total renin release. But the latter effect may be offset by concurrent baroreceptor-mediated release of total renin (mostly prorenin) when blood-pressure is lowered.

Adult↗
PubMed1977

Plasma prorenin in normal, hypertensive, and anephric subjects and its effect on renin measurements.

We have previously shown that a cryoactivatable inactive form of renin, which we have tentatively termed prorenin, occurs in human plasma. Plasma prorenin is measured by subtracting the endogenous plasma renin activity (PRA) from the total renin activity measured after cryoactivation. Cryoactivation is accomplished by shaking plasma at -5 degrees C for 4 days. Circulating prorenin averaged 5.6 +/- 0.8 (SE) ng/ml per hour in a group of 30 normal subjects and 5.1 +/- 1.0 ng/ml per hour in 25 hypertensive subjects during random sodium intake. In these two groups, prorenin ranged from zero to 36 times the endogenous renin level, averaging 2.5-fold in normal subjects and 3.4-fold in hypertensive subjects. During sodium deprivation prorenin more than doubled in 12 hypertensive subjects from a mean of 2.8 to 6.3 ng/ml per hour. In 25 anephric subjects, circulating prorenin was slightly lower than in normal subjects, averaging 3.4 +/- 0.9 ng/ml per hour (P less than 0.05). In contrast to our findings in nephric subjects, the low level of PRA measured in anephric subjects ((0.26 +/- 0.04 ng/ml per hour) was almost always a constant fraction of the measured prorenin. This led to the demonstration that prorenin can be inadvertently activated by chilling blood during processing for renin measurement and this often accounts for the small amount of renin measured in plasmas from anephric subjects. The error in routine PRA measurements due to inadvertent activation averaged +48% in anephric subjects and +17% in those with kidneys. Evaluation of the effect of processing bloods at room temperature revealed that net angiotensin I accumulation is less than 2% of that generated during incubation and can be ignored. Accordingly, to avoid the inadvertent activation of prorenin which can at times lead to a sizable and variable overestimation of PRA we recommend collecting and processing blood samples at room temperature and then storage of plasma completely frozen until the time for analysis.

Adolescent↗