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The Npr1 gene-knockout ( Npr1<jats:sup>\u2212\/\u2212<\/jats:sup>) mice showed 30\u201335 mmHg higher systolic blood pressure (SBP) and a 63% greater heart weight-to-body weight (HW\/BW) ratio compared with wild-type ( Npr1<jats:sup>+\/+<\/jats:sup>) mice. The mRNA levels of both angiotensin-converting enzyme and angiotensin II type 1a receptor were increased by three- and fourfold, respectively, in Npr1<jats:sup>\u2212\/\u2212<\/jats:sup>null mutant mice hearts compared with the wild-type Npr1<jats:sup>+\/+<\/jats:sup>mice hearts. In parallel, the expression levels of interleukin-6 and tumor necrosis factor-\u03b1 were increased by four- to fivefold, in Npr1<jats:sup>\u2212\/\u2212<\/jats:sup>mice hearts compared with control animals. The NF-\u03baB binding activity in nuclear extracts of Npr1<jats:sup>\u2212\/\u2212<\/jats:sup>mice hearts was increased by fourfold compared with wild-type Npr1<jats:sup>+\/+<\/jats:sup>mice hearts. Treatments with captopril or hydralazine equally attenuated SBP; however, only captopril significantly decreased the HW\/BW ratio and suppressed cytokine gene expression in Npr1<jats:sup>\u2212\/\u2212<\/jats:sup>mice hearts. The ventricular cGMP level was reduced by almost sixfold in Npr1<jats:sup>\u2212\/\u2212<\/jats:sup>mice compared with wild-type control mice. The results of the present study indicate that disruption of NPRA\/cGMP signaling leads to the augmented expression of cardiac RAS pathways that promote the development of cardiac hypertrophy and remodeling.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00079.2007","type":"journal-article","created":{"date-parts":[[2007,6,14]],"date-time":"2007-06-14T04:08:40Z","timestamp":1181794120000},"page":"193-202","source":"Crossref","is-referenced-by-count":30,"title":["Genetic disruption of guanylyl cyclase\/natriuretic peptide receptor-A upregulates ACE and AT1 receptor gene expression and signaling: role in cardiac hypertrophy"],"prefix":"10.1152","volume":"31","author":[{"given":"Elangovan","family":"Vellaichamy","sequence":"first","affiliation":[{"name":"Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of 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