C-type natriuretic peptide (CNP) is produced by the vascular smooth muscle cells (SMCs) of injured and atherosclerotic arteries, in which it may exert autocrine control over SMCs by binding to its principal receptors, NPR-B and NPR-C, but few studies have examined the factors that regulate CNP expression in human SMCs. In the present report, we show that serum induces significant increases in both CNP and NPR-C transcript levels in human, but not rat SMCs in culture, and that pretreatment with either the general tyrosine kinase inhibitor genistein, the platelet-derived growth factor (PDGF) tyrosine kinase inhibitor AG 1296, or the protein kinase C (PKC) inhibitor GF109203X blocks most of the serum-induced increase in CNP. PDGF-BB also induced significant dose-dependent increases in CNP transcript that correlated temporally with the serum effect on CNP mRNA. Inhibition of several PDGF-BB signaling pathways downstream of receptor activation showed that PKC inhibition with GF109203X was almost as effective as genistein in abolishing the PDGF-BB-induced up-regulation of CNP mRNA. Furthermore, PKC activation by phorbol 12-myristate 13-acetate (PMA) produced an extremely high level of CNP mRNA that was abolished by GF109203X. Immunoreactive CNP was markedly increased in SMCs receiving 10% serum, 20 ng/ml PDGF-BB, or PMA, and was decreased in PDGF-treated and PMA-treated cells by AG 1296 and GF109203X, respectively. This report suggests that in humans, PDGF and other factors signaling through receptor tyrosine kinases and downstream activation of PKC could represent an important control for CNP expression in vascular smooth muscle.
Anorectal disorders can generate considerable patient discomfort and disability. Although mortality due to such complaints is very low, it is important for the clinician to maintain a high index of suspicion for systemic illness caused by an anorectal source. A detailed history and physical examination should be performed, and the need for imaging or procedures should be assessed. This review examines the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes for patients with anorectal disorders. Figures show the important structures of the anal canal; differences in the anatomy of the origin of internal and external hemorrhoid venous supplies; depictions of a typical anodermal linear tear; Foley catheter–assisted rectal foreign body removal technique; and pertinent anatomy related to a prolapsed rectum through the anus; and types and locations of anorectal abscesses and fistulas. Tables list common painful and painless anorectal disorders; key differences in anal canal structures above and below the pectinate line; anal symptoms mistakenly attributed to hemorrhoids; internal hemorrhoidal grading, description, and recommended treatment; Rome III criteria for the diagnosis of constipation; and a summary of anorectal conditions. This review contains 6 highly rendered figures, 6 tables, and 80 references. Keywords: functional constipation; PEG; abdominal radiographs; pediatric constipation
Anorectal disorders can generate considerable patient discomfort and disability. Although mortality due to such complaints is very low, it is important for the clinician to maintain a high index of suspicion for systemic illness caused by an anorectal source. A detailed history and physical examination should be performed, and the need for imaging or procedures should be assessed. This review examines the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes for patients with anorectal disorders. Figures show the important structures of the anal canal; differences in the anatomy of the origin of internal and external hemorrhoid venous supplies; depictions of a typical anodermal linear tear; Foley catheter–assisted rectal foreign body removal technique; and pertinent anatomy related to a prolapsed rectum through the anus; and types and locations of anorectal abscesses and fistulas. Tables list common painful and painless anorectal disorders; key differences in anal canal structures above and below the pectinate line; anal symptoms mistakenly attributed to hemorrhoids; internal hemorrhoidal grading, description, and recommended treatment; Rome III criteria for the diagnosis of constipation; and a summary of anorectal conditions. This review contains 6 highly rendered figures, 6 tables, and 80 references. Keywords: functional constipation; PEG; abdominal radiographs; pediatric constipation
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