The Role of Recurrent Insulin-Induced Hypoglycemia on Renal Prostanoid Production
Wael A. Alanazi
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
Selim Fakhruddin
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
Keith E. Jackson *
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
*Author to whom correspondence should be addressed.
Abstract
Aims: The present study was performed to evaluate the effect of recurrent insulin induced hypoglycemia (RIIH) on renal prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) production during hypoglycemia-induced hypertension.
Study Design: In the current study, renal microdialysis was adapted as a sampling tool to evaluate the changes in renal interstitial prostanoids.
Place and Duration of Study: Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe between September 2015 – August 2016.
Methodology: Male Sprague Dawley rats were treated for two weeks with 7U/kg subcutaneous insulin injections. On the 14th day, the hypoglycemic animals were divided into three groups (7U+vehicle), (7U+captopril), and (7U+NS398), and surgeries were performed. The carotid artery, jugular vein and bladder were cannulated for hemodynamic evaluation, drugs infusion and urine collection respectively. Microdialysis probes were inserted into the renal cortex and physiological saline was infused through the probe and dialysate was harvested. A 4 hour control period was then performed and followed by a 4 hour treatment period with vehicle, captopril (12 mg/kg) or NS398 (0.3 mg/kg) bolus infusions. The renal interstitial samples were analyzed for 6-keto-PGF1α (the stable PGI2 metabolite) and TXB2 (the stable TXA2 metabolite) by ELISA.
Results: During hypoglycemia, the mean arterial pressure (MAP) was increased from 92±0.54 mmHg (day 0) to 142±1.08 mmHg (day 14) as compared to the saline treated group. The hypoglycemia-induced hypertension promoted the renal production of 6-keto-PGF1α (187±31 pg/ml) and TXB2 (382±35 pg/ml) as compared to saline treated animals keto-PGF1α (69±6.0 pg/ml) and TXB2 (172±10 pg/ml). Captopril and NS398 treatment blocked 6-keto-PGF1α (90±16 pg/ml and 63±12pg/ml respectively) when compared to the 7U+vehicle treated group (195±33 pg/ml). TXB2 was inhibited during captopril and NS398 treatment (211±28, and 128±23 pg/ml respectively) as compared to 7U+vehicle treated group (357±38 pg/ml).
Conclusion: These results demonstrated that RIIH induces prostanoids formation by renal AngII elevation which in turn enhances COX2 activity in the kidney.
Keywords: Angotensin II, COX2, hypoglycemia, microdialysis, prostanoids, RIIH