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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary excretion of tissue kallikrein is reduced in essential hypertension. Although a similar finding has been reported in spontaneously hypertensive rats (SHR), only a few studies have been concerned with the amount of enzyme within the kidney both at the time of onset and during progression of the hypertension. We have performed an ontogenic study on the renal parenchymal values and immunoreactivity of tissue kallikrein in Okamoto SHR aged 4-78 weeks. Additionally, these two parameters were analysed in human biopsies taken from patients with hypertensive nephropathy. The enzymatic activity of renal tissue kallikrein (active and total; specifically antagonized by anti-tissue kallikrein antibodies), increased from 4 to 52 weeks in SHR when compared to normotensive Wistar Kyoto (WKY) rats; this increase was associated with a significant increase in blood pressure. In contrast, 78 weeks SHR and human biopsy tissue showed a substantial reduction in tissue kallikrein values. Also, both renal tissues showed a reduction in immunoreactivity in the cells of the connecting tubules that specifically store the enzyme. In advanced hypertension the observed reduction in tissue kallikrein was probably secondary to a loss of distal tubular mass, as a result of tubular atrophy and fibrosis. The greater values for renal tissue kallikrein in the kidney and reported reduced urinary excretion during the early phases of spontaneous hypertension may be explained by a primary defect in the mechanisms that regulate release of tissue kallikrein from the connecting tubule cells.
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PMID:An ontogenic study of renal tissue kallikrein in Okamoto spontaneously hypertensive rats: comparisons with human hypertensive nephropathy. 132 Feb 31

1. This study aims to further elucidate the role of the tissue and plasma kallikrein-kinin systems in blood pressure, electrolyte and volume homoeostasis. Components thereof and of the renin-angiotensin-aldosterone system were measured in conjunction with frusemide administration, in normotensive subjects and in patients with primary hypertension. 2. Frusemide increased plasma pre-kallikrein, angiotensin II and aldosterone concentrations and plasma renin activity, whereas the plasma level of tissue kallikrein remained unchanged. Basal values and the induced changes were similar in both groups. 3. Frusemide increased the urine volume and the excretion of Na+, K+, Mg2+, Cl-, aldosterone, prostaglandin E2 and tissue kallikrein. These changes were similar in both groups, but the total tissue kallikrein excretion was significantly lower in the hypertensive patients. Excretion of electrolytes and hormones was also measured during three 24 h urine collection periods and did not differ between the two groups. 4. Thus, acute administration of frusemide to hypertensive patients and normal subjects increased the plasma level of pre-kallikrein, possibly indicating less activation to kallikrein and subsequently less kinin generation in the blood stream. This also suggests a role for the plasma kallikrein-kinin system in the regulation of vascular tone and blood volume. Circulating tissue kallikrein does not seem to be acutely involved. 5. Urinary excretion of kallikrein is reduced in patients with primary hypertension after the administration of frusemide, apparently without affecting the renal excretory response.
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PMID:Plasma and tissue kallikrein-kinin systems during acute administration of frusemide in normotensive and hypertensive humans. 165 30

Vasoactive hormones acting as endocrine, neuroendocrine, or local hormonal systems (intracrine, autocrine, and paracrine) are an important component of the many factors that regulate blood pressure. Hypertension may be the result of an alteration in the balance between vasodepressor and vasopressor hormonal systems. Changes in this balance could be due to genetic factors such as mutations in one of the genes of the vasoactive system or environmental factors that alter the synthesis and release of one or more vasoactive hormones. Endocrine and neuroendocrine vasopressor hormonal systems, such as the renin-angiotensin system and catecholamines, play a well-established and important role in the regulation of blood pressure and the pathogenesis of some secondary forms of hypertension. The blockade of such systems has already resulted in effective antihypertensive treatment. The role of local hormonal systems is less well established; however, recent evidence suggests they also play an important role in the regulation of blood pressure and the pathogenesis of hypertension. Some vasopressor hormonal systems, such as the renin-angiotensin system, can act as both endocrine or local hormonal systems. Work using transgenic rats harboring the mouse Ren-2 gene has conclusively demonstrated that the renin-angiotensin system, acting as a local hormonal system, has the capability to cause severe hypertension. Whether this model of experimental hypertension mimics any type of human hypertension is not known. Vasodepressor hormones such as kinins, prostaglandins, and endothelium-derived relaxing factor (EDRF) act mainly as local hormonal systems, with the notable exception of atrial natriuretic factor, which may act as both an endocrine and a local hormone. The tissue kallikrein-kinin system, acting either directly or via paracrine eicosanoids or EDRF, participates in local regulation of the circulation, renal function, and the acute antihypertensive effect of angiotensin converting enzyme inhibitors. A restriction fragment length polymorphism (RFLP) that distinguishes the kallikrein gene family of a strain of spontaneously hypertensive rats (SHR) from normotensive Brown Norway rats has been identified. In a set of 32 recombinant inbred strains derived from these SHR and Brown Norway strains, the RFLP marking the kallikrein gene family of SHR cosegregated with an increase in blood pressure. Also, in a study of Utah families it was found that a dominant-allele kallikrein gene expressed as high urinary kallikrein excretion was associated with a decreased risk of essential hypertension. In conclusion, vasopressor and vasodepressor hormones, acting not only as endocrine but also as local hormones, play an important role in the regulation of blood pressure and the pathogenesis of hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Local hormonal factors (intracrine, autocrine, and paracrine) in hypertension. 188 59

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

The evidence presented here suggests strongly that the kallikreins-kininogens-kinins-kininase II system has most significant role in regulation of systemic BP. This system is involved in mediation and modulation of renin-angiotensin-aldosterone, PGS and vasopressin in the regulation of sodium water balance, renal hemodynamic and BP. Therefore, reduction in the kinin-formation due to high production of kininase II, and lower formation of tissue kallikrein might result in an increased release of vasoconstrictor angiotensin II on one side, and on the other side much reduced production of PGE, vasodilator. These changes might lead to deranged vascular smooth muscle structures and cell membrane functions, retention of sodium and water, increased plasma volume, and renovascular constriction. These physiological defects might result in the development of essential hypertension (Fig. 4). Although, it is possible now to treat hypertensive conditions with tissue kallikrein and kininase II inhibitors. These discoveries have opened up new vistas to research on the pharmacological applications of kallikreins-kininogens-kinins-kininases in human diseases.
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PMID:Interrelationship between the kallikrein-kinin system and hypertension: a review. 328 Mar 99

The stimuli generating kinins participating in blood pressure, volume and sodium homeostasis and their origin are not fully known. We studied the effects of a combined sodium and volume load on circulating plasma and tissue kallikreins. Normal saline (2000 ml) was infused over 4 h in 14 subjects with primary hypertension and 15 age- and sex-matched normotensive control subjects. The infusion increased blood pressure slightly in both groups. Plasma prekallikrein levels fell in both groups (normotensives: 98 +/- 4 to 87 +/- 5%, p = 0.002; hypertensives: 106 +/- 5 to 94 +/- 6%, p = 0.003), but more rapidly in normotensives. Circulating tissue kallikrein did not change significantly in the normotensive group but was reduced in the hypertensive group. Sodium excretion during the infusion correlated negatively with changes in plasma prekallikrein and positively with plasma levels of tissue kallikrein in the normotensive group only. Urinary tissue kallikrein excretion during the infusion increased significantly only in the normotensive group. The levels or changes of circulating prekallikrein and tissue kallikrein were not related to the levels or changes in blood pressure in any of the groups. In the hypertensive group there was a negative correlation between blood pressure changes and urinary sodium and tissue kallikrein excretion. Thus, in normotensive subjects an acute sodium and volume load appears to activate the plasma kallikrein system and the activation correlates with sodium excretion. There are subtle differences in subjects with primary hypertension. The relevance of these differences with respect to the pathogenesis of primary hypertension remains to be evaluated.
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PMID:Circulating kallikreins during sodium chloride infusion in normal and hypertensive humans. 918 Dec 53

Human tissue kallikrein gene polymorphisms were identified in the promoter region by polymerase chain reaction (PCR) and DNA sequencing. One polymorphic region was identified between nucleotides -121 and -133 with respect to the transcription initiation site of the tissue kallikrein gene. Ten alleles with length and nucleotide sequence variations were detected among 108 unrelated Caucasians, African-Americans, and Asians. The polymorphisms show Hardy-Weinberg equilibrium. Allele-specific amplification and PCR analyses were used to detect the various forms of polymorphism. The promoter activity was analyzed in human embryonic kidney 293 cells by transient transfection assays. Sequential 5'-deletion analysis of the tissue kallikrein gene promoter revealed that the region from -144 to -98 is crucial for its promotor activity, while alleles D and H had significantly lower promoter activities than the other alleles in the -940/+10 deletion constructs. The high variability and the proximity to the tissue kallikrein gene render it suitable for application as a new tool in genetic studies for evaluation of the tissue kallikrein gene in the pathogenesis of human essential hypertension.
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PMID:DNA polymorphisms in the 5'-flanking region of the human tissue kallikrein gene. 918 64

The aim of the study was to evaluate if short-term mineralocorticoid administration activates the circulating kallikrein-kinin systems in normotensive humans and patients with hypertension. Fludrocortisone was given daily for 1 week and circulating components of the plasma and tissue kallikrein-kinin systems and renin-angiotensin-aldosterone system were measured repeatedly. Fludrocortisone increased blood pressure in the normotensive group. A significant reduction in circulating pre-kallikrein and increase in tissue kallikrein occurred only in the normotensive group. Changes in blood pressure in the normotensive group correlated negatively with changes in plasma pre-kallikrein and positively with changes in circulating tissue kallikrein. In the hypertensive group the correlation with pre-kallikrein was non-significant and with tissue kallikrein negative. We conclude that short-term administration of fludrocortisone in moderate doses to normotensive humans induces changes compatible with increased activity in the circulating plasma and tissue kallikrein-kinin systems and that this activation may be abnormal in subjects with primary hypertension.
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PMID:Circulating kallikreins in normotensive and hypertensive humans: effects of mineralocorticoid administration. 929 8

Kinins lower blood pressure but the stimuli leading to kinin generation and their origin are less well known. We administered angiotensin II in graded infusion doses to patients with primary hypertension and normotensive controls to study the effects of on circulating kallikreins. Angiotensin II infusion did not significantly alter plasma prekallikrein or tissue kallikrein levels and the plasma levels and their changes did not correlate with blood pressure levels or changes. In the normotensive group prekallikrein levels and renin activity correlated negatively with urinary sodium and chloride excretion during basal conditions and partially during the infusion. U-tissue kallikrein concentration increased in the normotensive group. Thus, acute elevation of blood pressure induced by angiotensin II does not activate the circulating kallikrein-kinin systems. Data rather indicate that the circulating kallikrein-kinin systems may be related to alterations in volume and sodium balance and that these mechanisms may be altered in primary hypertension.
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PMID:Circulating plasma prekallikrein and tissue kallikrein in normotensive and hypertensive humans: effects of angiotensin II infusion. 960 85

Hypertension that results in left ventricular (LV) hypertrophy and/or fibrosis can lead to cardiac dysfunction. Spontaneously hypertensive rats (SHR) develop high blood pressure and LV hypertrophy at an early age and are a popular model of human essential hypertension. To investigate the role of the tissue kallikrein-kinin system in cardiac remodeling, an adenovirus containing the human tissue kallikrein gene was injected intravenously into adult SHR and normotensive Wistar-Kyoto (WKY) rats. The blood pressure of WKY rats remained unchanged throughout the experiment. Alternatively, kallikrein gene transfer reduced blood pressure in SHR for the first 2 wk, but had no effect from 3 to 5 wk. Five weeks after kallikrein gene delivery, SHR showed significant reductions in LV-to-heart weight ratio, LV long axis, and cardiomyocyte size; however, these parameters were unaffected in WKY rats. Interestingly, cardiac collagen density was decreased in both SHR and WKY rats receiving the kallikrein gene. Kallikrein gene transfer also increased cardiac capillary density in SHR, but not in WKY rats. The morphological changes after kallikrein gene transfer were associated with decreases in JNK activation as well as transforming growth factor (TGF)-beta 1 and plasminogen activator inhibitor-1 levels in the heart. In addition, kallikrein gene delivery elevated LV nitric oxide and cGMP levels in both rat strains. These results indicate that kallikrein-kinin attenuates cardiac hypertrophy and fibrosis and enhances capillary growth in SHR through the suppression of JNK, TGF-beta 1, and plasminogen activator inhibitor-1 via the nitric oxide-cGMP pathway.
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PMID:Kallikrein gene delivery attenuates cardiac remodeling and promotes neovascularization in spontaneously hypertensive rats. 1281 55


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