endothelin-1 and Streptococcal-Infections

Endothelin-1 (ET-1), the most potent vasoconstrictor peptide, is known to play a role in arterial hypertension. In patients with acute poststreptococcal glomerulonephritis (APSGN) an increase in the production of ET-1 is suspected due to damaged endothelium, platelet activation and increased thrombin production in the glomeruli. The aim of the present study was to investigate whether the levels of plasma ET-1 are elevated in children with APSGN. Furthermore, we examined the association between plasma ET-1 levels and blood pressure levels in the same children.. We studied 18 children (14 boys) with APSGN (mean age 7.44 to approximately 2.82 years). Fourteen healthy children served as controls. The following parameters were evaluated: plasma ET-1, plasma atrial natriuretic peptide (ANP), plasma renin (Rn), serum aldosterone (Aldo), creatinine clearance (Ccr) and fractional excretion of sodium (FENa).. The mean plasma ET-1 concentrations were higher in patients with APSGN (3.39 to approximately 1.86 pg/mL) compared to controls (1.40 to approximately 0.15 pg/mL; P=0.0001). Patients with APSGN also had higher plasma ANP concentrations (41.67 to approximately 27.99 pg/mL) than the controls (22.80 to approximately 4.24 pg/mL; P=0.011). Plasma Rn concentrations were lower in patients (24.54 to approximately 16.34 microU/mL) compared to controls (56.76 to approximately 32.36 microU/mL; P=0.027). A positive correlation was found between ET-1 plasma concentrations and the height of systolic or diastolic blood pressure (r=0.57, P=0.013 and r=0.53, P=0.023, respectively).. Our results suggest that increased plasma ET-1 concentrations may play an important role in the pathogenesis of hypertension in children with acute poststreptococcal glomerulonephritis.

Topics: Acute Disease; Child; Endothelin-1; Female; Glomerulonephritis; Humans; Hypertension; Male; Streptococcal Infections

Endothelin-1 can cause pulmonary vasoconstriction via endothelin-A (ET(A)) receptor activation. We hypothesized that ET(A) blockers (EMD 122946 and BQ 610) would reduce hypoxia-induced (HYP) but not group B streptococcal infusion (GBS)-induced pulmonary hypertension in a juvenile whole animal model. Pulmonary hypertension was created by exposing chronically instrumented piglets to HYP (n = 12) or heat-killed GBS (n = 11). ET(A) blockade was produced by increasing bolus doses of EMD122946 or BQ 610. Pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), left atrial pressure, central venous pressure, and cardiac output were continuously measured. Pulmonary and systemic vascular resistance indices (PVRI and SVRI) were calculated. HYP doubled PAP and PVRI. Both ET(A) blockers decreased PAP and PVRI in a dose-dependent manner in HYP, with high doses decreasing PVRI to baseline and reducing PAP by 50%. GBS also doubled both PAP and PVRI. EMD 122946 did not change PAP or PVRI in GBS, although BQ 610 markedly increased PVRI (>100% increase with 0.15 mg/kg) and showed a trend toward increasing PAP. Both models showed minimal (<25%) changes in SAP or SVRI. Neither ETA blocker changed baseline hemodynamics in the absence of HYP or GBS. PaO(2) did not change with GBS but decreased with BQ 610. ET(A) receptor blockade attenuated hypoxic, but not GBS induced pulmonary hypertension. BQ 610 worsened PVRI and oxygenation in the GBS model. Differences in response to ET(A) blockade in pulmonary hypertension may be seen depending on the etiology (hypoxia versus infection-associated), and the specific ET(A) antagonist used.

Topics: Animals; Blood Pressure; Carbon Dioxide; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Humans; Hypertension, Pulmonary; Hypoxia; Infant, Newborn; NG-Nitroarginine Methyl Ester; Oligopeptides; Oxygen; Pulmonary Circulation; Receptor, Endothelin A; Streptococcal Infections; Streptococcus agalactiae; Sus scrofa; Thiazoles

To elucidate the possible roles of nitric oxide (NO), endothelin-1 (ET-1), and reactive oxygen species (ROS) in the pathophysiology of serogroup A streptococcal (GAS) peritoneal sepsis, we investigated the effects of aminoethylisothiourea (AE-ITU), an inducible NO synthase (iNOS) inhibitor, and a ROS scavenger, and the ET-1 receptor antagonist bosentan. In rats, live GAS inocula, 3 x 10(8) and 1 x 10(9) cfu/kg, entailed a 24-h mortality of 10% and 90%, respectively. GAS caused increases in tissue iNOS activity (9 h), in serum nitrite/nitrate (9-24 h), and in intracellular leukocyte ROS levels (3-6 h). These changes were all prevented by the pre-treatment with AE-ITU. A novel finding was that AE-ITU also prevented the GAS-induced marked increase in plasma ET-1 at 6 h. Short-term (7-h) survival was improved by both AE-ITU and by bosentan. The mechanism(s) for the beneficial effects of AE-ITU may possibly be a combined mode of action; iNOS inhibition, ROS scavenging, and inhibition of the increase in plasma ET-1 caused by GAS.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Bosentan; Endothelin Receptor Antagonists; Endothelin-1; Enzyme Inhibitors; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Shock, Septic; Streptococcal Infections; Streptococcus pyogenes; Sulfonamides; Survival Rate; Thiourea; Time Factors