ENDOGENOUS ANGIOTENSIN-II MODULATES THE EFFECT OF ATRIAL-NATRIURETIC-PEPTIDE ON EXTRACELLULAR FLUID PARTITION

Atrial natriuretic peptide (ANP) has been shown to promote a fluid shi ft from the intravascular toward the interstitial compartment and to i nteract with the renin-angiotensin system at the renal as well as the extrarenal level. In the present studies, the interaction between the renin-angiotensin system and the effects of ANP infusion (100 ng.kg-1. min-1 for 45 min) on arterial pressure and hematocrit were assessed in bilaterally nephrectomized, anesthetized rats. In a first series of e xperiments, suppression of angiotensin II generation was achieved by c hronic (10 days) treatment by the angiotensin-converting-enzyme inhibi tor (ACEI) captopril in rats maintained on a low-sodium diet. ACEI pre treatment prevented the rise in hematocrit associated with ANP infusio n (+2.1 +/- 0.1 vs. +5.8 +/- 0.2%, P < 0.05), without influencing the effect of ANP on arterial pressure. In ACEI-pretreated rats, acute adm inistration of angiotensin II at a subpressor dose (2.5 ng.kg-1.min-1) restored the ANP-induced increase in hematocrit. In a second series o f experiments, acute blockade of the renin-angiotensin system was obta ined by the ACEI enalaprilat or the nonpeptide angiotensin II receptor antagonist losartan (both 1 mg/kg iv bolus). In the presence of eithe r enalaprilat or losartan, the ANP-induced increase in hematocrit was similarly prevented. These results indicate that the effect of ANP on vascular permeability is modulated by endogenous angiotensin II, possi bly due to distinct influences of the two peptides at the level of pre - and postcapillary resistances.