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

In 12 conscious dogs, we investigated whether the angiotensin II-receptor a ntagonist losartan increases renal sodium excretion and urine volume during controlled mechanical ventilation (CMV) with positive end-expiratory press ure. In four experimental protocols, the dogs were extracellular volume (EC V) expanded (electrolyte solution, 0.5 ml . g(-1) . min(-1) iv) or not and received losartan (100 mu g . kg(-1) . min(-1) iv) or not. They breathed sp ontaneously during the Ist and 4th hour and received CMV with positive end- expiratory pressure (mean airway pressure 20 cmH(2)O) during the 2nd and 3r d hours. In the expansion group, dogs with losartan excreted similar to 18% more sodium (69 +/- 7 vs. 38 +/- 5 mu mol . min(-1) kg(-1)) and 15% more u rine 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 mu mol min-l kg-l) 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 aldo sterone 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(-1) during CMV in nonexpan ded dogs without losartan. Mean arterial pressure decreased by 10 mmHg in n onexpanded dogs with losartan. In conclusion, losartan increases sodium exc retion and urine volume during CMV if the ECV is expanded. If the ECV is no t expanded, a decrease in mean arterial blood pressure and/or an increase i n aldosterone and vasopressin during CMV attenuates the renal effects of lo sartan.