{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:32:30Z","timestamp":1791203550566,"version":"4.2.0"},"edition-number":"1","reference-count":324,"publisher":"Wiley","isbn-type":[{"value":"9780470650714","type":"electronic"}],"license":[{"start":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T00:00:00Z","timestamp":1301616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autocrine, paracrine, endocrine, and neuroendocrine hormonal systems help regulate cardio\u2010vascular 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\u2010angiotensin 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.<\/jats:p><jats:p>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<jats:italic>via<\/jats:italic>autacoids such as eicosanoids, nitric oxide (NO), endothelium\u2010derived 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\u2010converting enzyme (ACE) and angiotensin type 1 receptor blockers (ARB).<\/jats:p><jats:p>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\u2010kinin\u2010system (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. B<jats:sub>2<\/jats:sub>\u2010KO 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\u2010salt\u2010induced hypertension).<\/jats:p><jats:p>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<jats:italic>via<\/jats:italic>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<jats:italic>via<\/jats:italic>release of NO, while drugs that activate the angiotensin type 2 receptor act in part<jats:italic>via<\/jats:italic>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. \u00a9 2011 American Physiological Society.<jats:italic>Compr Physiol<\/jats:italic>1:971\u2010993, 2011.<\/jats:p>","DOI":"10.1002\/cphy.c100053","type":"other","created":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T22:25:52Z","timestamp":1301696752000},"page":"971-993","source":"Crossref","is-referenced-by-count":90,"title":["The Kallikrein\u2010Kinin System as a Regulator of Cardiovascular and Renal Function"],"prefix":"10.1002","author":[{"given":"Nour\u2010Eddine","family":"Rhaleb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Ping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar A.","family":"Carretero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1","volume-title":"The Kinin System (The Handbook of Immunopharmacology)","author":"Farmer SG","year":"1997"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000090323.58122.5C"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000228997.88162.a8"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.30.2.217"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:26:2-3:185"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0901-1003"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/35024095"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.37.26079"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.135459"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1076"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(81)90262-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5349"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200523669"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.20.1.74"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20021708"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(85)91434-2"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.06.063"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000015608.37608.18"},{"key":"e_1_2_6_20_1","first-page":"F408","article-title":"Renal hemodynamics in response to a kinin analogue antagonist","volume":"255","author":"Beierwaltes WH","year":"1988","journal-title":"Am J Physiol"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-186-42588"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.8.11.971"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.8.11.1089"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.14.1.73"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000131497.73744.1a"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.6.593"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02630706"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(00)00107-1"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199015061-00010"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.41.4.26"},{"key":"e_1_2_6_31_1","first-page":"H1370","article-title":"Harken AH, Banerjee A. 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