ABSTRACT
INTRODUCTION: Activation of the renin-angiotensin system which is common in diabetes mellitus might affect heme oxygenase (HO-1) gene expression. AIM: Assessment of the effects of administration of angiotensin II (Ang II) receptor antagonist (losartan) with HO-1 inducer or inhibitor on erectile signaling in diabetic rats. MATERIALS AND METHODS: Seventy male rats were divided equally into seven groups; healthy controls, streptozotocin-induced diabetic rats, rats on citrate buffer, diabetic rats on losartan, diabetic rats on HO-1 inducer (cobalt protoporphyrin [CoPP]), diabetic rats on losartan and CoPP, and diabetic rats on losartan and HO-1 inhibitor (stannus mesoporphyrin [SnMP]). MAIN OUTCOME MEASURE: HO enzyme activity, HO-1 gene expression, cyclic guanosine monophosphate (cGMP) assay, intracavernosal pressure (ICP), and cavernous tissue sinusoids surface area. RESULTS: HO-1 gene expression, HO enzymatic activity, and cGMP were significantly decreased in the cavernous tissue of diabetic rats. These parameters were significantly elevated with the use of CoPP that restored the normal control levels of HO enzyme activity. Administration of losartan exhibited a significant enhancing effect on these parameters compared with the diabetic group, but not restored to the control levels, whereas administration of CoPP combined with losartan led to the restoration of their normal levels. ICP demonstrated significant decline in diabetic rats. The use of CoPP and/or losartan led to its significant improvement compared with diabetic rats. Administration of either losartan and/or CoPP led to a significant increase in the cavernous sinusoids surface area of diabetic rats. Administration of losartan with SnMP significantly decreased the enhancing effect of losartan on the studied parameters. CONCLUSION: The decline in erectile function in diabetes mellitus could be attributed to the downregulation of HO-1 gene expression. HO-1 induction added to Ang II receptor antagonist could improve erectile function.
Subject(s)
Antihypertensive Agents/pharmacology , Diabetes Mellitus, Experimental/complications , Erectile Dysfunction/diagnosis , Heme Oxygenase-1 , Losartan/pharmacology , Penile Erection/drug effects , Animals , Antihypertensive Agents/administration & dosage , Carrier Proteins , Disease Models, Animal , Erectile Dysfunction/etiology , Erectile Dysfunction/physiopathology , Gene Expression , Heme Oxygenase-1/antagonists & inhibitors , Heme Oxygenase-1/drug effects , Heme Oxygenase-1/genetics , Intracellular Signaling Peptides and Proteins , Losartan/administration & dosage , Male , RNA/genetics , Rats , Reverse Transcriptase Polymerase Chain Reaction , Treatment OutcomeABSTRACT
BACKGROUND: The purpose of this study was to investigate the effect of mesenchymal stem cells (MSCs) on cardiovascular complications of type 1 diabetes mellitus (DM) in rats. MATERIAL/METHODS: MSCs were derived from the bone marrow of male albino rats. The MSCs were characterized morphologically and by RT-PCR for CD29 expression. They were then infused into female rats which were made diabetic by IP injection of streptozotocin (STZ). The rats were divided into control, STZ, and STZ plus MSC groups. Serum insulin, glucose, and fibrinogen were estimated in all groups and the Y-chromosome gene sry was detected by PCR in pancreatic and cardiac tissues. Physiological cardiovascular functions (heart rate, systolic blood pressure) were assessed by a Langendorff apparatus. RESULTS: Diabetic rats which received MSCs showed significantly lower serum glucose and increased serum insulin levels compared with the STZ group. Improvement of cardiovascular performance was also observed in the STZ/MSC group compared with the STZ group. The sry gene was detected by PCR in the pancreatic and cardiac tissues of the STZ/MSC group. CONCLUSIONS: Rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling blood glucose level in diabetic rats. This may provide a source of cell-based therapy for DM. Furthermore, MSC transplantation can improve cardiac function in DM.<
