Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma kallikrein releases bradykinin when activated by gram-negative septicemia or irreversible hemorrhagic shock. Pancreatitis releases glandular kallikrein causing hypotension and increased vascular permeability. Bradykinin in the brain produces hypertension. Renal kallikrein is released by high arterial pressure, vasodilators, low doses of noradrenaline, angiotensin II, mineralocorticoids and rapid volume expansion. It has a biphasic relation to sodium excretion. In essential hypertension, kallikrein release into the blood and urine is low and facilitates hypertension. High renin in Bartter's syndrome is balanced by high PGE and kallikrein without hypertension.
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PMID:Kallikrein, kininogen and kinins in control of blood pressure. 37 13

Brown Norway kininogen-deficient rats had very low levels of plasma kininogens and lower levels of plasma prekallikrein, compared with those of normal rats of the same strain. Systolic blood pressure, determined by the tail-cuff method, of 5-week-old kininogen-deficient rats (106 +/- 0.4 mm Hg, n = 7) and the rate of systolic blood pressure increase with age were not different from those in normal rats. Weekly injections of deoxycorticosterone acetate (5 mg/kg s.c.) with 1% sodium chloride solution in drinking water after uninephrectomy at 7 weeks of age caused a gradual increase in the blood pressure of normal rats, reaching a plateau at 18 weeks of age, whereas that of deficient rats rose rapidly to 158 +/- 6 mm Hg 2 weeks after the start of treatment and continued to increase slightly, becoming significantly higher than normal rats at 8, 9, 10, 11, and 12 weeks of age (p less than 0.05 or 0.01). The levels of urinary prokallikrein and active kallikrein were slightly higher in deficient rats before deoxycorticosterone acetate-salt treatment but were not significantly increased after this treatment, whereas these levels in normal rats were increased 3.6- and 4.7-fold by this treatment. Urinary free kinin, collected from the ureter in untreated deficient rats, was below the detection limit. The plasma level of low molecular weight kininogen, the substrate of glandular kallikrein, was decreased in normal rats during the treatment. Continuous subcutaneous injection of aprotinin by an osmotic pump to normal rats induced significant increase in blood pressure. These results indicate that glandular kallikrein may play a suppressive role in deoxycorticosterone acetate-salt hypertension.
Hypertension 1991 Jun
PMID:Suppression of rat deoxycorticosterone-salt hypertension by kallikrein-kinin system. 171 Jun 5

A 44-year-old woman with a history of cerebral infarction and hypertension developed sudden onset of speech and visual disturbance. On admission, her general physical examinations showed high blood pressure of 210/120 mmHg and Raynaud's phenomena. The neurological examinations revealed right upper quadratic hemianopsia, left oculomotor nerve paresis and left hyperreflexia. Laboratory findings showed that antinuclear and anti-DNA antibodies were positive. The activity of Fletcher factor was reduced to 50%, and the activated partial thromboplastin time (APTT) was prolonged to 82.6 seconds. And a 1:1 dilution with normal plasma failed to correct the prolonged APTT, indicative of circulating anticoagulant to Fletcher factor. Plasma fibrinogen increased to 500 mg/dl but FDP was normal. The CT scan demonstrated the recurrently developed cerebral infarction in the left occipital lobe. Cerebral angiogram revealed mild atherosclerosis of basilar and bilateral posterior cerebral arteries, but any occlusive lesions were not found. Although she had a history of hypertension, this case suggests the possibility that the disturbance in fibrinolytic system may have been caused by the circulating anticoagulant to Fletcher factor, and contributed to her cerebral infarctions.
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PMID:[A case of cerebral infarction with circulating anticoagulant to Fletcher factor]. 191 33

Alterations in activity of kaolin-activated (contact-activated, CA) and immunoreactive (IR) prekallikrein were studied in blood plasma of healthy persons and of patients with hypertension under conditions of rest and of dose-dependent physical loading. CA prekallikrein was dissimilarly altered depending on the type of hemodynamic structure of the pressure reaction (arterial pressure): content of CA prekallikrein was increased in hyperkinetic type and--decreased in hypokinetic type. Content of IR prekallikrein, measured by means of radial immunodiffusion using monospecific antiserum, was similar in healthy persons and in the patients at rest and after physical exercises. It was increased slightly but did not correlate with CA prekallikrein alterations. As content of CA- and IR-prekallikreins did not correlate in the disease dynamics and after physical exercises, functional impairments may cause activation of blood plasma prekallikrein in hypertension. A procedure for isolation of highly purified preparation of kallikrein, production of monospecific antiserum to prekallikrein are described. Immunochemical studies and quantitative estimation of IR-prekallikrein were carried out.
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PMID:[Contact-activated and immunoreactive prekallikrein in the plasma of patients with hypertension]. 311 Oct 85

The mechanism of activation of inactive renin was studied in normal human plasma. The molecular weight of active renin and those of inactive renin before and after activation were analyzed by sephadex gel filtration. Active renin of human plasma had a molecular weight of 48,000 +/- 1000. Trypsin treatment and cold treatment activated inactive renin of a molecular weight of 54,000 +/- 1000. The inactive renin apparently did not change its molecular weight after activation. "Cryoactivation" of inactive renin was possible only when whole plasma was used. When the whole plasma was fractionated by gel filtration, cryoactivation was not observed in any of the fractions. Cryoactivation requires certain plasma factor(s) contained in some fractions. Plasma kallikrein is likely to be a major factor required for the cryoactivation of inactive renin, whereas some other factors may also participate in this mechanism.
Hypertension
PMID:Studies on the activation and molecular weight of inactive renin in human plasma. 699 73

Renin and prorenin concentrations in plasma correlate closely, but the proportion of active renin to prorenin shows some variation in different forms of hypertension. The proportion of active renin to prorenin is higher in normal renin essential hypertensives and in patients with renal hypertension than in normal subjects, and it is lower in low renin essential hypertension and primary hyperaldosteronism. Plasma deficient in plasma prekallikrein shows a lower proportion of active renin than might be expected. Active renin and plasma angiotensin II concentration show a strong correlation while prorenin correlates weakly with plasma angiotensin II concentration.
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PMID:Relation between renin and prorenin in plasma from hypertensive patients and normal people: evidence for different renin:prorenin ratios. 747 33

The dynamics was analysed of changes of arterial blood pressure, plasma kininogen and prekallikrein concentrations and plasma renin activity (PRA) in 50 patients with arterial hypertension, in relation to the type of blood pressure response to captopril. It was shown that after three weeks of treatment with captopril 150 mg daily, in 23 patients (46%) normalization of systolic and diastolic blood pressure occurred, and in 27 patients (54%), despite a significant reduction, blood pressure normalization was not achieved. In both groups of patients a significant decrease of plasma kininogen concentration and an increase of plasma prekallikrein level were found, indicating kininogenase activation and PRA increase. However, only in patients with arterial blood pressure normalization, a return of kininogen concentration to normal value was observed and a twofold increase of PRA in relation to the initial value was noted. Our studies indicate that in patients with arterial hypertension treated with captopril a correlation appears between the changes of plasma kinin system and PRA which determines the mode of blood pressure reaction to captopril.
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PMID:[Concentrations of kininogen and prekallikrein in plasma and activity of plasma renin depending on the type of blood pressure response to captopril in patients with arterial hypertension]. 794 72

Increased levels of hemostatic factors may play a role in the pathogenesis of myocardial infarction by triggering thrombin formation. We measured factor XII (FXII), factor XI (FXI), plasma prekallikrein (PK) and high-molecular-weight kininogen (HK) in 200 patients having survived myocardial infarction for at least 2 months, and in 100 healthy controls. We found significantly elevated levels of FXI clotting activity (FXI:C), HK:C and of the amidolytic activity of PK (PK:Am) among the patients as compared to the controls. Plasma levels of FXI:C, HK:C and PK:Am in the highest quartile were associated with an odds ratio of 1.9 (95% CI: 1.0-3.8), 2.0 (95% CI: 1.0-4.0) and 5.4 (95% CI: 2.6-11.2), respectively, compared to the respective plasma levels in the lowest quartile. After correction for established clinical and laboratory risk factors, the association between PK:Am plasma levels and myocardial infarction remained significant (P=0.0007). Combination of high PK:Am plasma levels and smoking or arterial hypertension, respectively, resulted in a more than additive relative risk for myocardial infarction.
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PMID:Elevated levels of plasma prekallikrein, high molecular weight kininogen and factor XI in coronary heart disease. 1188 8

The plasma kallikrein-kinin system (KKS) plays a critical role in human physiology. The KKS encompasses coagulation factor XII (FXII), the complex of prekallikrein (PK) and high molecular weight kininogen (HK). The conversion of plasma prekallikrein to kallikrein by the activated FXII and in response to numerous different stimuli leads to the generation of bradykinin (BK) and activated HK (HKa, an antiangiogenic peptide). BK is a proinflammatory peptide, a pain mediator and potent vasodilator, leading to robust accumulation of fluid in the interstitium. Systemic production of BK, HKa with the interplay between BK bound-BK receptors and the soluble form of HKa are key to angiogenesis and hemodynamics. KKS has been implicated in the pathogenesis of inflammation, hypertension, endotoxemia, and coagulopathy. In all these cases increased BK levels is the hallmark. In some cases, the persistent production of BK due to the deficiency of the blood protein C1-inhibitor, which controls FXII, is detrimental to the survival of the patients with hereditary angioedema (HAE). In others, the inability of angiotensin converting enzyme (ACE) to degrade BK leads to elevated BK levels and edema in patients on ACE inhibitors. Thus, the mechanisms that interfere with BK liberation or degradation would lead to blood pressure dysfunction. In contrast, anti-kallikrein treatment could have adverse effects in hemodynamic changes induced by vasoconstrictor agents. Genetic models of kallikrein deficiency are needed to evaluate the quantitative role of kallikrein and to validate whether strategies designed to activate or inhibit kallikrein may be important for regulating whole-body BK sensitivity.
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PMID:Human plasma kallikrein-kinin system: physiological and biochemical parameters. 1968 62

Activation of angiotensin II type 2 receptors (AT(2)R) causes the release of kinins, which have beneficial effects on the cardiovascular system. However, it is not clear how AT(2)R interact with the kallikrein-kinin system to generate kinins. Prolylcarboxypeptidase is an endothelial membrane-bound plasma prekallikrein activator that converts plasma prekallikrein to kallikrein, leading to generation of bradykinin from high-molecular-weight kininogen. We hypothesized that AT(2)R-induced bradykinin release is at least in part mediated by activation of prolylcarboxypeptidase. Cultures of mouse coronary artery endothelial cells were transfected with an adenoviral vector containing the AT(2)R gene (Ad-AT(2)R) or green fluorescent protein only (Ad-GFP) as control. We found that overexpression of AT(2)R increased prolylcarboxypeptidase mRNA by 1.7-fold and protein 2.5-fold compared with Ad-GFP controls. AT(2)R overexpression had no effect on angiotensin II type 1 receptor mRNA. Bradykinin release was increased 2.2-fold in AT(2)R-transfected cells. Activation of AT(2)R by CGP42112A, a specific AT(2)R agonist, increased bradykinin further in AT(2)R-transfected cells. These effects were diminished or abolished by AT(2)R blockade or a plasma kallikrein inhibitor. Furthermore, blocking prolylcarboxypeptidase with a small interfering RNA partially but significantly reduced bradykinin release by transfected AT(2)R cells either at the basal condition or when stimulated by the AT(2)R agonist CGP42112A. These findings suggest that overexpression of AT(2)R in mouse coronary artery endothelial cells increases expression of prolylcarboxypeptidase, which may contribute to kinin release.
Hypertension 2010 Sep
PMID:Role of prolylcarboxypeptidase in angiotensin II type 2 receptor-mediated bradykinin release in mouse coronary artery endothelial cells. 2060 3


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