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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distal tubules of the kidney express the full set of the components of the kallikrein-kinin system, which works independently from the plasma kallikrein-kinin system. Studies on the role of the renal kallikrein-kinin system, using congenitally kininogen-deficient Brown-Norway Katholiek rats and also bradykinin B2 receptor knockout mice, revealed that this system starts to function and to induce natriuresis and diuresis when sodium accumulates in the body as a result of excess sodium intake or aldosterone release, for example, by angiotensin II. Thus, it can be hypothesized that the system works as a safety valve for sodium accumulation. The large numbers of studies on hypertensive animal models and on essential hypertensive patients, particularly those with salt sensitivity, indicate a tendency toward the reduced excretion of urinary kallikrein, although this reduction is modified by potassium intake and impaired renal function. We hypothesize that the reduced excretion of the renal kallikrein may be attributable to a genetic defect of factor(s) in renal kallikrein secretion process and may cause salt-sensitive hypertension after salt intake.
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PMID:The renal kallikrein-kinin system: its role as a safety valve for excess sodium intake, and its attenuation as a possible etiologic factor in salt-sensitive hypertension. 1262 48

It is suggested that an ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein. We reported that glibenclamide, an ATP-sensitive potassium channel blocker, accelerated dose-dependent secretion of renal kallikrein in sliced kidney cortex and in vivo in rats. In vehicle-treated normal Brown- Norway-Kitasato (nBN-Ki) rats, the administration of glibenclamide increased urinary kallikrein secretion, but changed neither the systolic blood pressure nor the urinary sodium on low (0.3%) NaCl diets. Although on high (8%) NaCl diets, the systolic blood pressure of the nBN-Ki rats administrated glibenclamide was significantly lower (P<0.05). The urinary levels of kallikrein and sodium of the nBN-Ki rats administrated glibenclamide were significantly increased (P<0.05, glibenclamide vs. vehicle). A similar result was obtained with a kidney-selective ATP-sensitive potassium blocker, N,N'-dicyclohexyl-4-morpholinecarboxamidine (U18177), in SD rats. Mutant kininogen-deficient Brown-Norway Katholiek (muBN-Ka) rats fed high (8%) NaCl diets showed an increase in urinary kallikrein levels, but showed neither hypotensive nor natriuretic actions by glibenclamide. A bradykinin B(2) receptor antagonist, 8-[3-[N-(E)-3-(6-acetamidopyridin-3-yl) acryloylglyycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methylquinoline (FR173657), which was administrated to SD rats, together with glibenclamide, abolished the hypotensive and natriuretic effects of glibenclamide in high-sodium (8%NaCl) hypertension, despite an accelerated secretion of urinary kallikrein. Therefore, these results indicate that glibenclamide, an ATP-sensitive potassium channel blocker suppressed sodium-induced hypertension through sodium excretion from the kidney resulting from accelerated secretion of urinary kallikrein.
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PMID:An ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein. 1926 86

Autocrine, paracrine, endocrine, and neuroendocrine hormonal systems help regulate cardio-vascular and renal function. Any change in the balance among these systems may result in hypertension and target organ damage, whether the cause is genetic, environmental or a combination of the two. Endocrine and neuroendocrine vasopressor hormones such as the renin-angiotensin system (RAS), aldosterone, and catecholamines are important for regulation of blood pressure and pathogenesis of hypertension and target organ damage. While the role of vasodepressor autacoids such as kinins is not as well defined, there is increasing evidence that they are not only critical to blood pressure and renal function but may also oppose remodeling of the cardiovascular system. Here we will primarily be concerned with kinins, which are oligopeptides containing the aminoacid sequence of bradykinin. They are generated from precursors known as kininogens by enzymes such as tissue (glandular) and plasma kallikrein. Some of the effects of kinins are mediated via autacoids such as eicosanoids, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and/or tissue plasminogen activator (tPA). Kinins help protect against cardiac ischemia and play an important part in preconditioning as well as the cardiovascular and renal protective effects of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor blockers (ARB). But the role of kinins in the pathogenesis of hypertension remains controversial. A study of Utah families revealed that a dominant kallikrein gene expressed as high urinary kallikrein excretion was associated with a decreased risk of essential hypertension. Moreover, researchers have identified a restriction fragment length polymorphism (RFLP) that distinguishes the kallikrein gene family found in one strain of spontaneously hypertensive rats (SHR) from a homologous gene in normotensive Brown Norway rats, and in recombinant inbred substrains derived from these SHR and Brown Norway rats this RFLP cosegregated with an increase in blood pressure. However, humans, rats and mice with a deficiency in one or more components of the kallikrein-kinin-system (KKS) or chronic KKS blockade do not have hypertension. In the kidney, kinins are essential for proper regulation of papillary blood flow and water and sodium excretion. B2-KO mice appear to be more sensitive to the hypertensinogenic effect of salt. Kinins are involved in the acute antihypertensive effects of ACE inhibitors but not their chronic effects (save for mineralocorticoid-salt-induced hypertension). Kinins appear to play a role in the pathogenesis of inflammatory diseases such as arthritis and skin inflammation; they act on innate immunity as mediators of inflammation by promoting maturation of dendritic cells, which activate the body's adaptive immune system and thereby stimulate mechanisms that promote inflammation. On the other hand, kinins acting via NO contribute to the vascular protective effect of ACE inhibitors during neointima formation. In myocardial infarction produced by ischemia/reperfusion, kinins help reduce infarct size following preconditioning or treatment with ACE inhibitors. In heart failure secondary to infarction, the therapeutic effects of ACE inhibitors are partially mediated by kinins via release of NO, while drugs that activate the angiotensin type 2 receptor act in part via kinins and NO. Thus kinins play an important role in regulation of cardiovascular and renal function as well as many of the beneficial effects of ACE inhibitors and ARBs on target organ damage in hypertension.
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PMID:The kallikrein-kinin system as a regulator of cardiovascular and renal function. 2373 9


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