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)

Primary hypertension is associated with a lack in renal kallikrein activity which might be one of the reasons for the blood pressure elevation. Some smaller and partially uncontrolled studies suggested that an oral substitution of glandular kallikrein lowers blood pressure by a kinin-mediated vasodilation and increased natriuresis. To test this hypothesis we treated in two studies over 100 patients with untreated mild to moderate primary hypertension (WHO I-II) for 5 resp. 12 weeks in a double blind randomized and placebo controlled manner with 1800 U glandular kallikrein orally. Blood pressure measurements were performed according to the two study designs after 3 and 5 resp. 8 and 12 weeks of treatment sphymomanometrically in the day time course. No significant changes in blood pressure by kallikrein treatment could be observed at any time. Neither renal kallikrein excretion, renin and ACE-activity nor blood glucose concentration in diabetics or non-diabetics was changed. Thus, we could undoubtedly demonstrate that oral applied glandular kallikrein has no effect on primary hypertension.
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PMID:Lack of oral kallikrein in lowering systemic blood pressure in primary hypertension. 146 64

To prove the effect of aging on the synthesis of renin-angiotensin-aldosterone system, renal kallikrein-kinin system, prostaglandin (PG), and thromboxane (TX) which regulate blood pressure, normotensive subjects and patients with essential hypertension (EH) were investigated in the present study. Although plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were decreased with aging in both groups, there is no significant differences between each groups while compared among each age-groups. Urinary excretion of kallikreins (active, inactive and total) in EH were decreased with aging as similar extent to that of normal subjects. There was no age-related change of kallikrein activation ratio in EH in contrary to normal subjects. In comparison with each age-group, the amount of urinary kallikrein excretion in EH were already small in young age-groups. The amount of urinary PGE2 excretion in female EH group was smaller than that of normal subjects, and there were no age-related changes in both groups. Urinary excretion of TXB2 and 11-dehydro-TXB2, which are the urinary major metabolites of TXA2 which has potent vasoconstrictive action, were increased in the age-group of 80-93 year-old both normal subjects and EH. There were no age-related change in both groups. Although these hypertensive vasoactive substances as renin, aldosterone and TXA2 in EH show the same profile as that in normal subjects, the synthesis of renal antihypertensive vasoactive substances as kallikrein and PGE2 in EH already decrease in younger patients. These results suggest that the lower activities of renal antihypertensive system is a cause of the development of hypertension.
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PMID:[The investigation about age-related changes in vasoactive substances of normal subjects and of patients with essential hypertension]. 163 30

Since the reduced kallikrein excretion demonstrated in essential hypertension suggested the possibility of an impairment in the renal kallikrein-kinin system, we decided to evaluate the efficacy and safety of oral kallikrein administration (glandular kallikrein derived from porcine pancreas) in 30 essential hypertensive subjects (21 males, 9 females, age range 34-62 years). Twenty subjects took 150 IU kallikrein t.i.d. for eight days; during this period their sodium intake remained normal (120 mEq Na+/die). Ten subjects took placebo. After the trial period, urinary kallikrein in the active group increased from 0.9 +/- 0.4 U/24 h (normal value greater than 1.2 U/24 h) to 1.6 +/- 1 U/24 h (p less than 0.05); systolic and diastolic blood pressure decreased respectively from 154.6 +/- 13.8 mmHg to 140.3 +/- 12.5 mmHg (p less than 0.01) and from 92.5 +/- 1.5 mmHg to 86 +/- 3.9 mmHg (p less than 0.025); urinary sodium and potassium excretion increased respectively from 96.7 +/- 17 mEq/24 h to 119.1 +/- 32.3 mEq/24 h (p less than 0.05) and from 36.7 +/- 11 mEq/24 h to 43.5 +/- 12.8 mEq/24 h (p less than 0.05). One patient in the kallikrein group suffered a transient episode of gastric pain. No modifications of the parameters evaluated were observed in the placebo group. We conclude that kallikrein has a mild hypotensive effect in hypertensive subjects and is generally well-tolerated. Its antihypertensive effect is probably due to the sodiuretic action of the substance.
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PMID:[The efficacy and tolerance of orally administered kallikrein in patients with essential arterial hypertension]. 180 83

Doxazosin, a new quinazoline-derivative postsynaptic alpha 1-adrenoceptor antagonist, was studied in this randomized, double-blind, placebo-controlled 12-week study. Its effects on blood pressure (BP), heart rate, metabolic functions and renal hormones were analyzed after administration of a single oral morning dose in a 3-phase fashion when administered to 17 patients (11 women, 6 men, 21 to 59 years) with mild to moderate uncomplicated essential hypertension. After titrating the antihypertensive effective dose biweekly from 1 to 8 mg/day and a mean end titration-point dose of 4.14 +/- 0.1 mg (mean +/- standard error of the mean) at week 8 of treatment, it was adjusted to maintain diastolic BP at levels less than or equal to 90 mm Hg for up to 12 weeks of treatment when, at a final mean dose of 4.35 +/- 0.2 mg/day, BP decreased in all patients by a mean 31 +/- 3/17 +/- 2 (supine) and 39 +/- 3/15 +/- 3 (standing) mm Hg (p less than 0.005) with no increase in heart rate and no "first-dose phenomenon." Neither the renin-aldosterone system nor electrolyte excretion was significantly affected. Renal function and metabolic parameters also remained unchanged. Urinary kallikrein excretion was augmented 2.47-fold (p less than 0.002). There was good tolerance; 1 patient discontinued the study because of dry nose. These results suggest that long-term monotherapy with doxazosin is an effective and safe antihypertensive agent for mild to moderate essential hypertension that stimulates urinary kallikrein excretion.
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PMID:Effects of doxazosin on blood pressure, renin-angiotensin-aldosterone and urinary kallikrein. 182 6

Reduced kallikrein excretion has been demonstrated in essential hypertension, suggesting an impairment of the renal kallikrein-kinin system. Therefore, we evaluated the efficacy and safety of oral kallikrein administration (glandular kallikrein derived form porcine pancreas) in 20 essential hypertensives (14 males and 6 females) aged between 34 and 62 years. Kallikrein was administered (150 U.I. three times daily) over a period of eight days, under normal sodium intake (120 mEq of Na+/day). After the kallikrein administration period, urinary kallikrein resulted increased (from 0.9 +/- 0.4 U/24h, normal value greater than 1.2 U/24h, to 1.6 +/- 1 U/24h; p less than 0.05). Blood pressure decreased (systolic: from 154.6 +/- 13.8 mmHg to 140.3 +/- 12.5 mmHg; p less than 0.01--diastolic: from 92.5 +/- 1.5 mmHg to 86 +/- 3.9 mmHg; p less than 0.025), while urinary excretion of sodium (from 96.7 +/- 16 mEq/24h to 119.1 +/- 32.2 mEq/24h; p less than 0.05) and potassium (from 36.7 +/- 11 mEq/24h to 43.5 +/- 12.8 mEq/24h; p less than 0.05) increased after kallikrein administration. We observed only a transient episode of gastric pain. In conclusion, kallikrein administration has a mild hypotensive effect in hypertensive patients, and is generally well tolerated. The antihypertensive action is probably due to the natriuretic effect of kallikrein.
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PMID:[Oral administration of extracted kallikrein to patients with essential arterial hypertension]. 183 64

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

Hypertension that occurs before the age of 60 years is strongly aggregated in families, mostly due to genetic factors with weaker contributions from a shared family environment. Hypertension is probably a heterogeneous collection of overlapping subsets of pathophysiological mechanisms, such as dyslipidemia, obesity, hyperinsulinemia and cation metabolism. Highly heritable traits such as sodium-lithium countertransport, urinary kallikrein excretion and a body fat pattern index show evidence of major gene segregation in families with hypertension. They are thought to be intermediate phenotypes in the chain of pathophysiological events leading from specific genes to the distant phenotype of hypertension. They provide evidence of measurable contributions from single gene traits to the susceptibility to hypertension. Genetic linkage studies have suggested that other specific loci (e.g. histocompatibility leukocyte antigen, blood group MN and the haptoglobin protein) contribute to the susceptibility to hypertension. DNA sequencing has shown a point mutation for lipoprotein lipase that conveys susceptibility to lipid abnormalities, and possibly also hypertension, as seen in families with dyslipidemic hypertension. Further application of these approaches, especially in families that include multiple siblings with hypertension, shows promise of a true understanding of how the combined effects of a few specific genes, the polygenic background and selected environmental factors can lead to essential hypertension. This understanding should foster better tailored and more effective approaches to the prevention, diagnosis and treatment of hypertension.
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PMID:Multigenic human hypertension: evidence for subtypes and hope for haplotypes. 209 95

Despite their vasodilating action, calcium antagonists increase renal sodium excretion. To ascertain whether renal kallikrein plays a role in the renal effects of calcium antagonists, nifedipine (N) (10 mg orally) or placebo (P) was given to 17 male patients with mild to moderate essential hypertension during a 6-h infusion of either saline (S) or aprotinin (A) (2 X 10(6) KIU in 200 ml of saline). Blood pressure (BP) and heart rate (HR) were measured every 10 min, and blood samples were taken at -10, 0, 30, 60, 120, 240, 360 min for plasma renin activity (PRA), creatinine, and osmolarity determinations. Urinary kallikrein, aldosterone, creatinine, and electrolytes were measured in 6-h urine collections. The acute administration of N induced a significant systolic BP (SBP) and diastolic (DBP) fall and a transient PRA increase that peaked at 30 min and were not modified by A infusion. Urinary volume (+47%), Na+ (+54%) and Cl- (+58%) excretion were significantly enhanced by N. There were less pronounced and statistically not significant increases in urinary excretion of Ca2+ (+38%) and K+ (+29%). Infusion of A did not interfere with the natriuretic effect of N. Our data do not support the hypothesis that the kallikrein-kinin system plays an important role in mediating the renal effects of nifedipine in humans.
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PMID:Natriuretic effect of acute nifedipine administration is not mediated by the renal kallikrein-kinin system. 243 33

We studied two groups of hypertensive patients in order to ascertain whether the acute natriuretic effect of nifedipine is mediated by humoral factors such as renal kallikrein or atrial natriuretic factor (ANF). First, 17 patients with mild to moderate essential hypertension maintained on a 130-mmol/day diet, received either nifedipine (10 mg orally) or placebo during a 6-h infusion of the kallikrein inhibitor aprotinin (2 x 10(6) KIU) or saline as control. Aprotinin, while significantly reducing urinary kallikrein activity, did not interfere with the acute effects of nifedipine on blood pressure, heart rate, urinary volume, urinary Na+ and creatinine clearance. In another group of eight patients on a constant daily Na+ intake of 130 mmol and in the supine position, placebo or nifedipine (10 mg sublingually) were administered, and blood pressure, heart rate, plasma renin activity, plasma aldosterone and plasma ANF, urinary Na+, urine volume and creatinine clearance, were monitored for 2 h. While placebo did not induce changes in any of the above parameters, nifedipine administration induced a significant decrease in blood pressure and increase in urinary Na+, urine volume and creatinine clearance, and a significant rise in ANF levels, from 19.4 +/- 2.8 pg/ml to a maximum of 23.9 +/- 2.5 and 24.1 +/- 2.2 pg/ml (P less than 0.05) at 60 and 90 min, respectively. In conclusion, our data do not support a role for renal kallikrein as a humoral mediator of the natriuretic effect of calcium antagonists, but do not exclude the possibility that ANF might participate in the nifedipine-induced increase in sodium and water excretion.
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PMID:Studies on the natriuretic effect of nifedipine in hypertensive patients: increase in levels of plasma atrial natriuretic factor without participation of the renal kallikrein-kinin system. 245 Jan 87

Essential hypertension is a heterogeneous group of disorders with different causes. This report reviews approaches taken and results found in current studies of the genetic and environmental determinants of essential hypertension. Recent observations from the University of Utah Cardiovascular Genetics Research Clinic and published data from other studies are cited. Several biochemical tests show strong associations with hypertension and substantial major gene and/or polygenic determination including: urinary kallikrein excretion, intracellular sodium concentration, sodium-lithium countertransport, plasma haptoglobin phenotypes, MN blood groups, and familial dyslipidemia.
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PMID:Definition of genetic factors in hypertension: a search for major genes, polygenes, and homogeneous subtypes. 246 8


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