Effect of nicardipine and atriopeptin on transcapillary shift of fluid and proteins

The possibility that calcium antagonists may alter extracellular fluid partition, as already suggested for atrial natriuretic peptide (ANP), was explored in anephric anesthetized rats by measuring changes in hematocrit and plasma proteins during infusion of synthetic ANP-(103-126) and the dihydropyridine derivative nicardipine. In response to ANP (1 micrograms.kg-1.min-1) or nicardipine (0.1 microgram.kg-1.min-1), which had a similar effect on arterial pressure, hematocrit increased by 9 +/- 0.1 and 5.4 +/- 0.3%, respectively, whereas plasma protein concentration increased to a lesser extent (3.9 +/- 0.3 and 3.7 +/- 0.2%, respectively). The simultaneous infusion of ANP and nicardipine had no additive effect on hematocrit, whereas the effect on arterial pressure was markedly enhanced. In additional experiments, an attempt was made to estimate the vascular leak of albumin in various tissues, using a quantitative Evans blue technique. Both ANP and nicardipine increased dye extravasation in skeletal and cardiac muscle, whereas ANP but not nicardipine increased extravasation in intestine. No significant change was observed in brain, liver, and lungs. These results suggest that nicardipine and ANP reduce plasma volume by an extrarenal mechanism. This fluid shift, possibly resulting from hemodynamic changes at the capillary level, is associated with a marked transfer of plasma albumin out of the vascular compartment.