{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:34:15Z","timestamp":1772786055891,"version":"3.50.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1998,9]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014We evaluated whether kinins exert a protective action against the development of two-kidney, one clip (2K1C) hypertension, a model characterized by an activated renin-angiotensin system in the ischemic kidney and increased expression of the bradykinin (BK) B<jats:sub>2<\/jats:sub>receptor in the contralateral kidney. BK B<jats:sub>2<\/jats:sub>-receptor knockout (B<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>), wild-type (B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>), and heterozygous (B<jats:sub>2<\/jats:sub><jats:sup>+\/\u2212<\/jats:sup>) mice underwent clipping of the left renal artery, with the other kidney remaining untouched. Basal systolic blood pressure (SBP, via tail-cuff plethysmography) was higher in B<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>mice than in B<jats:sub>2<\/jats:sub><jats:sup>+\/\u2212<\/jats:sup>or B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>mice (121\u00b12 versus 113\u00b12 and 109\u00b11 mm Hg;<jats:italic>P<\/jats:italic>&lt;0.05 for both comparisons). SBP did not change from basal values after sham operation, but it increased in mice that underwent clipping. The increase in SBP was greater in 2K1C B<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>mice than in B<jats:sub>2<\/jats:sub><jats:sup>+\/\u2212<\/jats:sup>or B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>mice (28\u00b12 versus 14\u00b12 and 14\u00b12 mm Hg, respectively, at 2 weeks;<jats:italic>P<\/jats:italic>&lt;0.05 for both comparisons). Blockade of the BK B<jats:sub>2<\/jats:sub>receptor by Icatibant enhanced the pressure response to clipping in B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>mice (29\u00b12 mm Hg at 2 weeks). Intra-arterial mean blood pressure (MBP) was higher in 2K1C than in respective sham-operated mice, with the MBP difference being higher in B<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>mice (32 and 38 mm Hg, at 2 and 4 weeks, respectively), and higher in B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>mice given Icatibant (30 and 32 mm Hg) than in B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>mice without Icatibant (17 and 18 mm Hg). At 4 weeks, acute injection of an angiotensin type 1 receptor antagonist normalized the MBP of 2K1C hypertensive mice. A tachycardic response was observed 1 week after clipping in B<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>and B<jats:sub>2<\/jats:sub><jats:sup>+\/\u2212<\/jats:sup>mice, but this effect was delayed in B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>mice. However, the HR response to clipping in B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>mice was enhanced by Icatibant. Within each strain, heart weight to body weight ratio was greater in 2K1C hypertensive mice than in sham-operated control animals (B<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>: 5.7\u00b10.1 versus 5.2\u00b10.1; B<jats:sub>2<\/jats:sub><jats:sup>+\/+<\/jats:sup>: 5.1\u00b10.1 versus 4.5\u00b10.1;<jats:italic>P<\/jats:italic>&lt;0.01 for both comparisons). The clipped kidney weight to nonclipped kidney weight ratio was consistently reduced in mice with 2K1C hypertension. Our results indicate that kinins acting on the BK B<jats:sub>2<\/jats:sub>receptor exert a protective action against excessive blood pressure elevation during early phases of 2K1C hypertension.<\/jats:p>","DOI":"10.1161\/01.hyp.32.3.503","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"503-509","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Renovascular Hypertension in Bradykinin B<sub>2<\/sub>-Receptor Knockout Mice"],"prefix":"10.1161","volume":"32","author":[{"given":"Paolo","family":"Madeddu","sequence":"first","affiliation":[{"name":"From the Clinica Medica and Terapia Medica, Medical School (P.M.), and the Department of Animal Biology, Section of Pharmacology (A.F.M., B.S.), University of Sassari, Sassari, Italy; the National Laboratory of the National Institute of Biostructures and Biosystems (P.M., L.G., C.E.), Osilo, Italy; the Department of Nephrology, Max Delbruck Center (W.G., A.L.), Berlin Buch, Germany; and the Department of Vascular Pathology, Istituto Dermopatico dell\u2019Immacolata (C.E.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Franca","family":"Milia","sequence":"additional","affiliation":[{"name":"From the Clinica Medica and Terapia Medica, Medical School (P.M.), and the Department of Animal Biology, Section of Pharmacology (A.F.M., B.S.), University of Sassari, Sassari, Italy; the National Laboratory of the National Institute of Biostructures and Biosystems (P.M., L.G., C.E.), Osilo, Italy; the Department of Nephrology, Max Delbruck Center (W.G., A.L.), Berlin Buch, Germany; and the Department of Vascular Pathology, Istituto Dermopatico dell\u2019Immacolata (C.E.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Bonaria","family":"Salis","sequence":"additional","affiliation":[{"name":"From the Clinica Medica and Terapia Medica, Medical School (P.M.), and the Department of Animal Biology, Section of Pharmacology (A.F.M., B.S.), University of Sassari, Sassari, Italy; the National Laboratory of the National Institute of Biostructures and Biosystems (P.M., L.G., C.E.), Osilo, Italy; the Department of Nephrology, Max Delbruck Center (W.G., A.L.), Berlin Buch, Germany; and the Department of Vascular Pathology, Istituto Dermopatico dell\u2019Immacolata (C.E.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Gaspa","sequence":"additional","affiliation":[{"name":"From the Clinica Medica and Terapia Medica, Medical School (P.M.), and the Department of Animal Biology, Section of Pharmacology (A.F.M., B.S.), University of Sassari, Sassari, Italy; the National Laboratory of the National Institute of Biostructures and Biosystems (P.M., L.G., C.E.), Osilo, Italy; the Department of Nephrology, Max Delbruck Center (W.G., A.L.), Berlin Buch, Germany; and the Department of Vascular Pathology, Istituto Dermopatico dell\u2019Immacolata (C.E.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolkmar","family":"Gross","sequence":"additional","affiliation":[{"name":"From the Clinica Medica and Terapia Medica, Medical School (P.M.), and the Department of Animal Biology, Section of Pharmacology (A.F.M., B.S.), University of Sassari, Sassari, Italy; the National Laboratory of the National Institute of Biostructures and Biosystems (P.M., L.G., C.E.), Osilo, Italy; the Department of Nephrology, Max Delbruck Center (W.G., A.L.), Berlin Buch, Germany; and the Department of Vascular Pathology, Istituto Dermopatico dell\u2019Immacolata (C.E.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Lippoldt","sequence":"additional","affiliation":[{"name":"From the Clinica Medica and Terapia Medica, Medical School (P.M.), and the Department of Animal Biology, Section of Pharmacology (A.F.M., B.S.), University of Sassari, Sassari, Italy; the National Laboratory of the National Institute of Biostructures and Biosystems (P.M., L.G., C.E.), Osilo, Italy; the Department of Nephrology, Max Delbruck Center (W.G., A.L.), Berlin Buch, Germany; and the Department of Vascular Pathology, Istituto Dermopatico dell\u2019Immacolata (C.E.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Costanza","family":"Emanueli","sequence":"additional","affiliation":[{"name":"From the Clinica Medica and Terapia Medica, Medical School (P.M.), and the Department of Animal Biology, Section of Pharmacology (A.F.M., B.S.), University of Sassari, Sassari, Italy; the National Laboratory of the National Institute of Biostructures and Biosystems (P.M., L.G., C.E.), Osilo, Italy; the Department of Nephrology, Max Delbruck Center (W.G., A.L.), Berlin Buch, Germany; and the Department of Vascular Pathology, Istituto Dermopatico dell\u2019Immacolata (C.E.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.13.1.3"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.17.2.242"},{"key":"e_1_3_2_3_2","first-page":"646","volume":"23","year":"1993","unstructured":"Madeddu P, Pinna Parpaglia P, Demontis MP, Varoni MV, Fattaccio MC, Glorioso N. 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