Changes in Glomerular Filtration Rate and Renal Plasma Flow in Cirrhotic Rats During Converting Enzyme Inhibition

Ibarra, Fernando; Galceran, Tilde; Oddo, Elisabet Mónica; Arrizurieta, Elvira

doi:10.3109/08860229809045090

Cited by 6 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The untreated CBDL rats of the present study were markedly hypotensive. In fact, they tended to be more hypotensive than in several previous studies [32,[37][38][39][40]. However, this degree of hypotension is not a unique finding [41][42][43][44][45].…”

Section: Discussionmentioning

confidence: 55%

“…In addition, increased local quenching of NO by superoxide (suggested by the high intrarenal levels of F 2 -isoprostanes) may leave the kidney susceptible to the unopposed effects of these vasoconstrictors. The increase in intrarenal angiotensin II and ET may explain why angiotensinconverting enzyme inhibitors (ACEI) [40], or ET antagonists [69] improve renal hemodynamics in cirrhotic rats. However, the use of these agents is severely limited because blood pressure tends to fall precipitously.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin E prevents renal dysfunction induced by experimental chronic bile duct ligation

Ortiz¹,

Manriquez²,

Nath³

et al. 2003

Kidney International

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Vitamin E prevents renal dysfunction induced by experimental chronic bile duct ligation

Ortiz¹,

Manriquez²,

Nath³

et al. 2003

Kidney International

View full text Add to dashboard Cite

show abstract

“…Further assessment of the IV kinetic parameters indicated that the forward rate constant from the central to the tubular compartment (K 13 ) was an extremely rapid process. This is unsurprising when one considers that this rate constant essentially represented elimination from the central compartment via glomerular filtration, which is expected to be a rapid process (i.e., ≈20−30% renal plasma flow rate 23 ). The model parameters governing saturable reabsorption further supported the assertion that the tubular compartment mechanistically represented the proximal tubule and kinetically identical spaces.…”

Section: ■ Discussionmentioning

confidence: 99%

Mechanism-Based Pharmacokinetic Modeling of Absorption and Disposition of a Deferoxamine-Based Nanochelator in Rats

2022

View full text Add to dashboard Cite

Deferoxamine (DFO) is an effective FDA-approved iron chelator. However, its use is considerably limited by off-target toxicities and an extremely cumbersome dose regimen with daily infusions. The recent development of a deferoxamine-based nanochelator (DFO-NP) with selective renal excretion has shown promise in ameliorating animal models of iron overload with a substantially improved safety profile. To further the preclinical development of this promising nanochelator and to inform on the feasibility of clinical development, it is necessary to fully characterize the dose and administrationroute-dependent pharmacokinetics and to develop predictive pharmacokinetic (PK) models describing absorption and disposition. Herein, we have evaluated the absorption, distribution, and elimination of DFO-NPs after intravenous and subcutaneous (SC) injection at therapeutically relevant doses in Sprague Dawley rats. We also characterized compartment-based model structures and identified model-based parameters to quantitatively describe the PK of DFO-NPs. Our modeling efforts confirmed that disposition could be described using a three-compartment mamillary model with elimination and saturable reabsorption both occurring from the third compartment. We also determined that absorption was nonlinear and best described by parallel saturable and first-order processes. Finally, we characterized a novel pathway for saturable SC absorption of an ultrasmall organic nanoparticle directly into the systemic circulation, which offers a novel strategy for improving drug exposure for nanotherapeutics.

show abstract

“…and surgically prepared for a renal clearance experiment as described previously (Ibarra et al. ). The trachea was cannulated to facilitate breathing.…”

Section: Methodsmentioning

confidence: 99%

Concerted regulation of renal plasma flow and glomerular filtration rate by renal dopamine and NOS I in rats on high salt intake

Ibarra

Borghese

Majowicz

et al. 2017

Physiological Reports

Self Cite

View full text Add to dashboard Cite

Under high sodium intake renal dopamine (DA) increases while NOS I expression in macula densa cells (MD) decreases. To explore whether renal DA and NOS I, linked to natriuresis and to the stability of the tubuloglomerular feedback, respectively, act in concert to regulate renal plasma flow (RPF) and glomerular filtration rate (GFR). Male Wistar rats were studied under a normal sodium intake (NS, NaCl 0.24%) or a high sodium intake (HS, NaCl 1% in drinking water) during the 5 days of the study. For the last two days, the specific D1‐like receptor antagonist SCH 23390 (1 mg kg bwt−1 day−1, sc) or a vehicle was administered. HS intake increased natriuresis, diuresis, and urinary DA while it decreased cortical NOS I expression (P < 0.05 vs. NS), Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‐d) activity in MD (P < 0.001 vs. NS) and cortical nitrates+nitrites (NOx) production (NS 2.04 ± 0.22 vs. HS 1.28 ± 0.10 nmol mg protein−1, P < 0.01). Treatment with SCH 23390 to rats on HS sharply decreased hydroelectrolyte excretion (P < 0.001 vs. HS) while NOS I expression, NADPH‐d activity and NOx production increased (P < 0.05 vs. HS for NOS I and P < 0.001 vs. HS for NADPH‐d and NOx). SCH 23390 increased RPF and GFR in HS rats (P < 0.01 HS+SCH vs. HS). It did not cause variations in NS rats. Results indicate that when NS intake is shifted to a prolonged high sodium intake, renal DA through the D1R, and NOS I in MD cells act in concert to regulate RPF and GFR to stabilize the delivery of NaCl to the distal nephron.

show abstract

Changes in Glomerular Filtration Rate and Renal Plasma Flow in Cirrhotic Rats During Converting Enzyme Inhibition

Cited by 6 publications

References 19 publications

Vitamin E prevents renal dysfunction induced by experimental chronic bile duct ligation

Vitamin E prevents renal dysfunction induced by experimental chronic bile duct ligation

Mechanism-Based Pharmacokinetic Modeling of Absorption and Disposition of a Deferoxamine-Based Nanochelator in Rats

Concerted regulation of renal plasma flow and glomerular filtration rate by renal dopamine and NOS I in rats on high salt intake

Contact Info

Product

Resources

About