Chromogranin A (CGA) belongs to a family of highly acidic proteins which are co-stored and co-released with the catecholamines from the mammalian adrenal gland and occur in nmolar concentrations in the human circulation. A vascular function for the adrenomedullary released and circulating CGA has yet to be established. The present study reports on the novel vasoinhibitory effect of the N-terminal domain of the adrenomedullary CGA in isolated segments of the human internal thoracic artery (ITA) and saphenous vein (SV). The collective term vasostatin(s) refers to N-terminal fragments (CGA1-76 and CGA1-113) of apparent molecular weights 7 to 22 kD, to indicate their vascular inhibitory effects. The sustained contractions evoked by the potent vasoconstrictor peptide, endothelin-1 (ET-1) were suppressed when ITA and SV segments were preincubated for 15 min with vasostatins (72 nM). The vasoinhibitory effects were not dependent on an intact endothelium and suppression of the response to 35 nM ET-1 was approximately 77% and approximately 40% in endothelium-denuded ITA and SV segments, respectively. In endothelium-denuded SV segments the vasostatins suppressed the maximal sustained tension response but not the potency for ET-1, indicating that the vasostatin effect did not involve interference with ET-1 binding to its vascular receptor. Preincubation of endothelium-denuded SV segments with nifedipine (1 microM) inhibited the sustained response to ET-1 > or = 10 nM by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

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The aims of this study are to To assess the response and efficacy of melanocortin receptor agonist (ACTH) as a treatment for patients with refractory diabetic nephropathy . This study was performed on 50 diabetic patients who attended internal medicine department at banha university hospital. Patients with diabetic nephropathy presented with proteinuria more than 1gm/24hour urine collection and who are not responding to anti proteinuric measures for at least one month of treatment treated with synthetic ACTH allowing a 6 months follow-up. Outcome. The primary endpoint was the percentage of patients achieving a complete remission (<300mg/24 hours) within 6months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, eGFR. Results. After 6months of ACTH therapy, 29 patients (58%) had achieved a complete remission and nine patients had achieved partial remission (18%).Conclusion. ACTH gel stabilizes renal function and reduces urinary protein.