Renal and hemodynamic effects of losartan in conscious dogs during controlled mechanical ventilation.

In 12 conscious dogs, we investigated whether the angiotensin II-receptor antagonist losartan increases renal sodium excretion and urine volume during controlled mechanical ventilation (CMV) with positive end-expiratory pressure. In four experimental protocols, the dogs were extracellular volume (ECV) expanded (electrolyte solution, 0.5 ml ⋅ kg-1 ⋅ min-1iv) or not and received losartan (100 μg ⋅ kg-1 ⋅ min-1iv) or not. They breathed spontaneously during the 1st and 4th hour and received CMV with positive end-expiratory pressure (mean airway pressure 20 cmH2O) during the 2nd and 3rd hours. In the expansion group, dogs with losartan excreted ∼18% more sodium (69 ± 7 vs. 38 ± 5 μmol ⋅ min-1 ⋅ kg-1) and 15% more urine during the 2 h of CMV because of a higher glomerular filtration rate (5.3 ± 0.3 vs. 4.5 ± 0.2 ml ⋅ min-1 ⋅ kg-1) and the tubular effects of losartan. In the group without expansion, sodium excretion (2.0 ± 0.6 vs. 2.6 ± 1.0 μmol ⋅ min-1 ⋅ kg-1) and glomerular filtration rate (3.8 ± 0.3 vs. 3.8 ± 0.4 ml ⋅ min-1 ⋅ kg-1) did not change, and urine volume decreased similarly in both groups during CMV. Plasma vasopressin and aldosterone increased in both groups, and plasma renin activity increased from 4.9 ± 0.7 to 7.8 ± 1.3 ng ANG I ⋅ ml-1 ⋅ h-1during CMV in nonexpanded dogs without losartan. Mean arterial pressure decreased by 10 mmHg in nonexpanded dogs with losartan. In conclusion, losartan increases sodium excretion and urine volume during CMV if the ECV is expanded. If the ECV is not expanded, a decrease in mean arterial blood pressure and/or an increase in aldosterone and vasopressin during CMV attenuates the renal effects of losartan.