Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to further clarify the role of kallikrein-kinin and renin-angiotensin systems in the hypotensive mechanisms of the angiotensin-I converting enzyme inhibitor by using highly sensitive and specific radioimmunoassays in patients with essential hypertension. Captopril was administered for 14 days (chronic effect), and the acute effects of captopril, alacepril and ramipril were also studied in the in-patients with essential hypertension. All of these converting enzyme inhibitors rapidly decreased the blood pressure and plasma angiotensin II levels, and increased plasma and urinary kinin and plasma renin activity in the acute effect. Following the administration of captopril for 14 days, these decreases and increases were maintained. The change of blood pressure was significantly correlated negatively with that of plasma kinin levels and positively with that of plasma angiotensin II levels in both the acute and chronic effect of converting enzyme inhibitors. Urine volume and urinary sodium excretion were markedly augmented, while both the change of urine volume and that of urinary sodium excretion were negatively correlated with the change of blood pressure in the chronic effect. These findings suggest that the hypotensive effect of converting enzyme inhibitors might be caused by an increase of plasma kinin and a decrease of plasma angiotensin II, and in part by an augmentation of urine volume and urinary sodium excretion. In this drug treatment, the renal kallikrein-kinin system may also play some role in the increase of urine volume and urinary sodium excretion through the increased kinin in the kidney.
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PMID:Significance of kallikrein-kinin and renin-angiotensin systems in the hypotensive mechanism of angiotensin-I converting enzyme inhibitors in essential hypertensives. 253 50

We have explored the role of kallikrein-kinin system in essential hypertension using spontaneously hypertensive rats (SHR) as an animal model. A rat tissue kallikrein complementary (c) DNA (RSK 1105) was used as a probe in Southern blot hybridization to detect restriction fragment length polymorphisms (RFLPs) in SHR. Using 23 different restriction endonucleases, we have identified five RFLPs involving alterations in restriction fragment lengths for the restriction enzymes Bgl II, Dra I, Nde I, Sph I, and Bcl I. Three of the enzymes, Nde I, Sph I, and Bgl II, generate multiple polymorphic fragments. We have further mapped these RFLPs with two additional probes, both from the rat renal kallikrein gene RSKG 7. The 5' probe, consisting of sequences approximately 2000 base pair (bp) 5' of the first exon, recognizes RFLPs in DNA digested with Bcl I and Sph I. The 3' probe, approximately 4400 bp away from the fifth exon, recognizes polymorphic fragments in DNA digested with Bcl I, Dra I and Nde I. These findings indicate possible differences in tissue kallikrein genes or their regulatory regions in SHR that could contribute to the pathogenesis of hypertension in this animal model.
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PMID:Restriction fragment length polymorphisms mapped in spontaneously hypertensive rats using kallikrein probes. 257 14

Urinary kallikrein and potassium were excreted in parallel in not only static but also dynamic sodium states. Oral potassium load stimulated the release of urinary kallikrein in normotensive subjects and WHO stage I essential hypertensive patients. Stage II essential hypertensive patients had the lowest value of basal level of urinary kallikrein and showed no increase in urinary kallikrein by oral potassium load. These results suggest that the functional activity of renal kallikrein-kinin system decreases with the development of essential hypertension.
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PMID:Effect of oral potassium on urinary kallikrein excretion in essential hypertension. 261 52

The micro-heterogeneity due to varied N-linked oligosaccharides of both active- and pro-types of human urinary kallikrein (HUK) in normal subjects and some patients were investigated by the methods of serial lectin affinity chromatography and crossed affino-immunoelectrophoresis. In the case of both types of normal HUK, the species carrying tri- and/or tetra-antennary oligosaccharide(s), corefucosylated bi-antennary oligosaccharide(s), and bi-antennary oligosaccharides containing outer galactose residues and an N-acetylglucosamine residue linked beta 1,4 to a beta-linked mannose residue (bisecting N-acetylglucosamine residue) amounted to approximately 36, 33 and 17% of the total of each type of HUK, respectively. On the other hand, in some diseases, i.e. essential hypertension, Bartter's syndrome and acute pancreatitis, alterations of the chromatographic and electrophoretic patters were observed and are assumed to correspond to glycosylation changes in each HUK molecule.
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PMID:Characterization of N-linked oligosaccharides of human urinary kallikrein molecules. 261 54

The inheritance of 12-hour overnight total urinary kallikrein excretion and its association with family history of essential hypertension were studied in 405 normotensive adults and 391 youths in 57 Utah pedigrees. Total urinary kallikrein excretion was highly familial with 51% of the total variance attributable to a dominant allele for high total urinary kallikrein excretion and 27% attributable to the combined effects of polygenes and shared family environment. An estimated 28% of the population has one or two copies of the dominant allele for high total urinary kallikrein excretion (2.3 SD units higher than the low homozygotes). About 83% of the population could be assigned to one of the two genotypic populations. Individuals with the high total urinary kallikrein excretion genotype were significantly less likely to have one or two hypertensive parents (relative odds = 0.56, p = 0.042). We conclude that a dominant allele expressed as high total urinary kallikrein excretion may be associated with decreased risk of essential hypertension. Further studies should be performed to confirm this finding and to test for interactions between this apparently protective gene and other genetic and environmental determinants of essential hypertension.
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PMID:A gene for high urinary kallikrein may protect against hypertension in Utah kindreds. 291 Aug 12

To further clarify the role of the renal kallikrein-kinin system in essential hypertension, a sensitive and simple method for the determination of both human urinary kininase I and kininase II was established, and the system components were determined in patients. In the measurement of kininase activity, desalted urine samples were incubated with synthetic bradykinin, and the reaction was terminated with kininase inhibitors, ethylene diamine tetraacetic acid and phenanthroline. Thus, kininase activity was determined as the kinin-destroying capacity. Moreover, the specific inhibitor for kininase II, SQ14225, was applied for the separation of kininase I and kininase II activities. Daily urinary excretions of total kininase and kininase I activities were significantly higher in essential hypertensive patients than those in normotensive subjects, whereas no difference was observed in kininase II activity. As reported previously, daily excretions of urinary kallikrein and kinin simultaneously determined in these patients were significantly lower than excretions in normotensive subjects. From these results, it was suggested that not only decreased renal kallikrein, but also increased kininase activity, may play an important role in the suppression of the renal kallikrein-kinin system through the reduction of active kinin level in essential hypertension.
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PMID:Urinary excretions of kininase I and kininase II activities in essential hypertension. A sensitive and simple method for its kinin-destroying capacity. 301 73

In order to investigate the role of the renal kallikrein-kinin (K-K) system in normal (NRH) and low renin (LRH) subgroups of essential hypertension (EHT), daily urinary excretions of renal K-K system components including kallikrein (KAL), total KAL, pre-KAL, kinin (KIN) and kininase (total, I and II), were measured in 21 normotensives (NT) and 45 patients with EHT (NRH: 29, LRH: 16). Urinary KAL and KIN quantities, KAL activity, total and pre-KAL, and kininase (total, I and II) were measured by direct RIA, kininogenase assay, direct RIA of KAL after trypsin treatment, and KIN destroying capacity, respectively. The daily excretions of KAL quantity and activity, total and pre-KAL, and KIN were significantly lower in EHT than in NT. That of total kininase and kininase I were significantly higher in EHT than in NT while no significant difference was found in kininase I between EHT and NT. In comparing NRH and LRH, the urinary KAL activity and KIN were lower in LRH than in NRH, and kininase I was higher in LRH than in NRH. No significant difference, however, was found in total and pre-KAL, KAL quantity and kininase II between NRH and LRH. The ratio of KAL quantity/total KAL which reflects the conversion rate from pre-KAL in the kidney, did not show any significant difference among NT, NRH and LRH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comprehensive studies on the renal kallikrein-kinin system in essential hypertension. 302 78

Captopril effects were studied in 27 patients with second-stage essential hypertension following administration of a single 25 mg oral dose of the drug. Blood pressure (BP), blood angiotensin-1-converting enzyme (ACE) activity, active (APR) and inactive (IPR) plasma renin levels were measured every 30 minutes for 3 hours. Before and near the end of the acute test, urinary kallikrein and catecholamine excretions were measured, and systemic and regional hemodynamic changes assessed. BP decreased in 21 patients: 11 of those had low basal APR (group 1), and 10 had normal or moderately elevated APR (group 2). The greatest hypotensive effect was observed within 1.5 hours after the administration, coinciding with the most marked ACE inhibition. There was no significant intergroup difference with respect to the extent of the hypotensive effect. No correlation was found between the hypotensive effect and the degree of ACE inhibition. All patients showed significantly decreased arteriolar tone, increased venous distensibility, decreased total peripheral resistance, and expanded end diastolic volume, while their cardiac output and heart rate remained unaffected. Hypertensive patients with low APR gave no evidence of renin-angiotensin inhibition or kallikrein-kinin activation that might have accounted for the hemodynamic effect of captopril.
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PMID:[Mechanisms of the hypotensive action of captopril in essential hypertension]. 303 55

Possible differences in structure-function relationship of urinary kallikrein between normotensive and hypertensive individuals were analysed using two different assay systems which detect two distinct entities of the enzyme. A monospecific goat anti-human urinary kallikrein antibody was characterized by inhibition studies with the purified active enzyme and by trypsin activation of endogenous urinary prokallikrein. Analysis of the data revealed that the antibody is directed against active kallikrein by recognizing an epitope which is different from the catalytic site of the enzyme but which is being exposed together with the active site during trypsin activation of the proenzyme. A direct radioimmunoassay for urinary kallikrein was developed and correlated with the kinin generating activity of the enzyme by assessing endogenous active and trypsin activated kallikrein in the urine of normotensive and hypertensive subjects. Significant positive correlations were found between the two assays for both active and total kallikrein in normotensive and hypertensive subjects and the slopes of the respective regression lines were identical. These data do not provide evidence for a defective enzyme, a defective activation of the proenzyme or for the presence of an inhibitor of urinary kallikrein in essential hypertension.
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PMID:Correlation of two different assays for urinary kallikrein in normotensive and hypertensive subjects. 324 81

Patients with essential hypertension were randomized to treatment with either prazosin or pinacidil, a new direct-acting vasodilator. Factors that might modulate the antihypertensive response and result in pseudotolerance to these drugs were measured before initiation of therapy and following 12 weeks of treatment. Despite significant reductions in blood pressure, pinacidil and prazosin did not produce an increase in plasma volume, did not activate the renin-angiotensin-aldosterone system, and did not interfere with the renal kallikrein-kinin system. The data fail to reveal evidence of physiologic compensatory changes that would lead to the development of pseudotolerance.
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PMID:Comparative effects of pinacidil and prazosin on blood pressure, weight, plasma volume, the renin-angiotensin-aldosterone system, and the renal kallikrein-kinin system in patients with essential hypertension. 333 Sep 89


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