Nitric oxide prevents hypertension yet enhances proximal tubule Na reabsorption. Nitric oxide synthase is inhibited by asymmetric dimethylarginine (ADMA) that is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) whose type 1 isoform is expressed abundantly in the proximal tubule (PT). We hypothesize that ADMA metabolized by DDAH-1 inhibits fluid reabsorbtion (Jv) by the proximal tubule.
View Article and Find Full Text PDFBackground: Due to clinical benefits, delayed cord clamping (DCC) is recommended in infants born before 37 weeks gestational age. The objective was to institute a delayed cord clamping program and to evaluate clinical outcomes one year after initiation.
Methods: This study occured at Christiana Care Health System, a tertiary care facility with a 52 bed level 3 Neonatal Intensive Care Unit (NICU).
Purpose: PARP is essential for recognition and repair of DNA damage. In preclinical models, PARP inhibitors modulate topoisomerase I inhibitor-mediated DNA damage. This phase I study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
September 2012
Adenosine, acting on A(1)-receptors (A(1)-AR) in the nephron, increases sodium reabsorption, and also increases renal vascular resistance (RVR), via A(1)-ARs in the afferent arteriole. ANG II increases blood pressure and RVR, and it stimulates adenosine release in the kidney. We tested the hypothesis that ANG II-infused hypertension is potentiated by A(1)-ARs' influence on Na(+) reabsorption.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
November 2010
Glomerular tubular balance maintains a stable fractional solute and fluid reabsorption in the proximal tubule over a range of glomerular filtration rates. The mediators of this process are unknown. We tested the hypothesis that adenosine, produced in proximal tubule cells acting on adenosine type 1 receptors (A(1)-AR) promotes Na(+) and fluid uptake and mediates glomerular tubular balance.
View Article and Find Full Text PDFTubuloglomerular feedback regulation of glomerular filtration rate (GFR) is mediated by adenosine, which acts on type 1 receptors in the afferent arteriole to increase resistance. However, new findings in isolated mouse tissue suggest that adenosine also dilates the efferent arteriole, which would reinforce the ability of adenosine to reduce GFR. This new information extends the concept that adenosine acts as a paracrine agent on both afferent and efferent arterioles.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
February 2009
This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically intravenously, would increase tubular sodium reabsorption and cause hypertension. Glucose was infused for 6 days (14 mg.kg(-1).
View Article and Find Full Text PDFAm J Physiol Renal Physiol
November 2008
This study used 16 h/day measurement of renal blood flow (RBF) and arterial pressure (AP) to determine the role of nitric oxide (NO) in mediating the renal vasodilation caused by onset of type 1 diabetes. The AP and RBF power spectra were used to determine the autoregulatory efficiency of the renal vasculature. Rats were instrumented with artery and vein catheters and a Transonic flow probe on the left renal artery and were divided randomly into four groups: control (C), diabetes (D), control plus nitro-L-arginine methyl ester (L-NAME; CL), and diabetes plus L-NAME (DL).
View Article and Find Full Text PDF1. The relationship between sodium intake and blood pressure is affected differently by changes in angiotensin (Ang) II and preglomerular resistance, and this study measured that relationship to evaluate the link between nitric oxide and blood pressure early in diabetes. 2.
View Article and Find Full Text PDFOnset of diabetes increases plasma renin activity (PRA) and glomerular filtration rate (GFR), but blood pressure (BP) is normal. In this study, a 70% surgical reduction in kidney mass (RK) was used to decrease baseline GFR and to prevent hyperfiltration during diabetes, and angiotensin converting enzyme inhibitors (ACEI) were used to inhibit angiotensin II (AngII) production, to test the hypothesis that a balance between GFR and AngII is required for normal BP early in diabetes. Diabetes was induced with streptozotocin (STZ) (35 mg/kg intravenously); and after 7 days of hyperglycemia (range: 408 to 486 mg/dL), insulin was intravenously infused continuously for a 4-day normoglycemic recovery period.
View Article and Find Full Text PDFThe purpose of this study was to establish the roles of the myogenic response and the TGF mechanism in renal blood flow (RBF) control at the very earliest stages of diabetes. Mean arterial pressure (MAP) and RBF were measured continuously, 18 h/d, in uninephrectomized control and diabetic rats, and transfer function analysis was used to determine the dynamic autoregulatory efficiency of the renal vasculature. During the control period, MAP averaged 91 +/- 0.
View Article and Find Full Text PDFThe dependence of blood pressure on a balance between superoxide and nitric oxide may be amplified in diabetes. We have shown that the first occurrence of sustained hyperglycemia in type I diabetes causes hypertension when induced in rats that have had nitric oxide synthesis blocked chronically (L-NAME, 10 microg/kg per minute IV). This study used tempol (18 micromol/kg per hour IV) to test the hypothesis that superoxide mediates that hypertensive response.
View Article and Find Full Text PDF