atrial-natriuretic-factor and Escherichia-coli-Infections

Raised cytokine levels and a hypoperfusion-associated decrease in glomerular filtration rate (GFR) are hallmarks of the genesis of septic acute renal failure (ARF). Therefore, anti-inflammatory as well as renal vasodilating therapeutic strategies may afford renal protection during septic ARF. The present study was designed to determine the effects of administration of urodilatin, pentoxifylline and theophylline to improve renal function in an ex-vivo model of 'septic renal injury'.. Eight series of experiments were performed: no intervention, perfusion with a suspension containing Escherichia coli bacteria (strain 536/21); E. coli + 10 microg/l urodilatin, E. coli + 20 microg/l urodilatin, E. coli + 100 microM theophylline, E. coli + 100 microM pentoxifylline and E. coli + URO 20 microg/l given 90 min after start of perfusion. Renal vascular and glomerular functional parameters as well as TNF-alpha release were analyzed up to 180 min.. Perfusion with E. coli caused an acute deterioration of renal vascular and glomerular function. URO 20 microg/l and PTX decreased renal vascular resistance (RVR) from 83.7 +/- 18.4 to 9.2 +/- 1.1 and 8.6 +/- 2.2 mm Hg/ml/min/g kidney and increased renal perfusion flow rate (PFR) from 8.2 +/- 1.5 to 14.6 +/- 0.8 and 14.1 +/- 2.2 ml/min/g kidney. As a result, GFR improved from 102.1 +/- 15.6 to 442 +/- 48.3 and 525.8 +/- 57 microl/min/g kidney during treatment with URO 20 microg/l and PTX, respectively. Renal TNF-alpha release was significantly reduced by URO 20 microg/l (from 178 +/- 23 to 45.2 +/- 2 and 47 +/- 3 pg/ml) in the E. coli + URO 20 microg/l and by PTX in the E. coli + PTX group if added to the perfusion medium upon start of perfusion. Interestingly, URO 20 microg/l also decreased RVR significantly from 62.2 +/- 6.1 to 35.9 +/- 6.0 mm Hg/ml/min/g kidney, improved PFR from 5.4 +/- 1.0 to 8.7 +/- 1.0 ml/min/g kidney, increased GFR from 160 +/- 43.3 to 280.7 +/- 27.9 microl/min/g kidney, and decreased TNF-alpha release to 122 +/- 18 pg/ml if applied 90 min after induction of septic ARF. In contrast, URO 10 microg/l did not significantly increase urine flow and did not appear to significantly improve renal perfusion. Theophylline showed no beneficial effects at all.. This suggests that urodilatin and pentoxifylline might be useful to protect renal function if given before a septic renal insult. Additionally, treatment with urodilatin is capable of restoring renal function in early Gram-negative sepsis-induced ARF even if given after the septic insult.

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Disease Models, Animal; Escherichia coli Infections; Humans; Kidney; Male; Pentoxifylline; Peptide Fragments; Perfusion; Rats; Rats, Sprague-Dawley

This study was performed to integratively investigate the vasoregulatory response during standardized splanchnic hypoperfusion in pigs. Splanchnic perfusion was reduced to 50% of baseline by: haemorrhage by 20 and 40% of the estimated total blood volume; femoral venous infusion of live E. coli to establish sepsis of systemic origin; portal venous infusion of live E. coli to establish sepsis of splanchnic origin. Invasive haemodynamic monitoring and radioimmunoassay analyses of arterial plasma concentrations of angiotensin II, endothelin-1 and atrial natriuretic peptide were carried out. Acute hypovolaemia reduced systemic and splanchnic vascular resistances following transient increases and increased angiotensin II levels (+587%), whereas endothelin-1 and atrial natriuretic peptide levels did not change significantly. Systemic sepsis following femoral venous infusion of E. coli resulted in increased splanchnic vascular resistance and increased levels of angiotensin II (+274%), endothelin-1 (+134%) and atrial natriuretic peptide (+185%). Infusion of E. coli via the portal venous route induced an increase in splanchnic vascular resistance associated with particularly elevated levels of angiotensin II (+1770%) as well as increased endothelin-1 (+201%) and atrial natriuretic peptide (+229%) concentrations. Hypovolaemia and sepsis, although standardized with a predefined level of splanchnic hypoperfusion, elicited differentiated cardiovascular and vasopeptidergic responses. Sepsis, particularly of portal origin, notably increased splanchnic vascular resistance related to increased production of the vasoconstrictors angiotensin II and endothelin-1. The role of atrial natriuretic peptide as a vasodilator seems to be of subordinate importance in hypovolaemia and sepsis.

Topics: Acute Disease; Anesthesia; Angiotensin II; Animals; Atrial Natriuretic Factor; Endothelin-1; Escherichia coli Infections; Female; Femoral Vein; Hemorrhage; Hypovolemia; Male; Neuropeptides; Portal Vein; Sepsis; Splanchnic Circulation; Swine; Vasoconstrictor Agents