ENDOGENOUS ANGIOTENSIN-II BUT NOT ATRIAL-NATRIURETIC-PEPTIDE MODULATES THE EFFECT OF NICARDIPINE ON EXTRACELLULAR FLUID PARTITION IN THE RAT

Objective: Both atrial natriuretic peptide (ANP) and the dihydropyridi ne derivative nicardipine lower arterial pressure and induce a shift o f plasma fluid from the vascular towards the interstitial compartment. Because some calcium antagonists increase the plasma concentration of ANP, and the effect of ANP on transcapillary fluid shift requires the presence of angiotensin II, we examined the consequences of blocking the ANP and renin-angiotensin systems on the hypotensive and haemoconc entrating effects of nicardipine. Methods: We evaluated the effects of 45-min 0.1 or 1 mug/kg per min nicardipine infusion on arterial press ure and haematocrit in anaesthetized, acutely binephrectomized Sprague -Dawley rats. Results: Infusion of nicardipine resulted in a dose-depe ndent decrease in arterial pressure. Haematocrit increased by an amoun t corresponding to the decrease in plasma volume calculated for the re levant dose. In the presence of monoclonal anti-ANP antibodies the nic ardipine-induced changes in haematocrit and arterial pressure were not affected. In rats pretreated for 2 weeks with the angiotensin convert ing enzyme inhibitor enalapril, as well as in rats receiving the angio tensin II receptor antagonist losartan acutely, the nicardipine-induce d increase in haematocrit was abolished. In enalapril-treated rats the increase in haematocrit was entirely restored when angiotensin II was infused at a subpressor dose. The nicardipine-induced decrease in art erial pressure was not affected by pharmacological blockade of the ren in-angiotensin system. Conclusions: These results demonstrate that the transcapillary shift of fluid induced by nicardipine is independent o f ANP and requires the presence of a functional renin-angiotensin syst em, whereas its hypotensive action is independent of both ANP and angi otensin II.