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 dihydropyridine derivative nicardipine lower arterial pressure and induce a shift of 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 haemoconcentrating effects of nicardipine.


METHODS
We evaluated the effects of 45-min 0.1 or 1 micrograms/kg per min nicardipine infusion on arterial pressure and haematocrit in anaesthetized, acutely binephrectomized Sprague-Dawley rats.


RESULTS
Infusion of nicardipine resulted in a dose-dependent decrease in arterial pressure. Haematocrit increased by an amount corresponding to the decrease in plasma volume calculated for the relevant dose. In the presence of monoclonal anti-ANP antibodies the nicardipine-induced changes in haematocrit and arterial pressure were not affected. In rats pretreated for 2 weeks with the angiotensin converting enzyme inhibitor enalapril, as well as in rats receiving the angiotensin II receptor antagonist losartan acutely, the nicardipine-induced 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 arterial pressure was not affected by pharmacological blockade of the renin-angiotensin system.


CONCLUSIONS
These results demonstrate that the transcapillary shift of fluid induced by nicardipine is independent of ANP and requires the presence of a functional renin-angiotensin system, whereas its hypotensive action is independent of both ANP and angiotensin II.
Valentin
J P
JP
Department of Medicine, CHU, Lapeyronie Hospital, Montpellier, France.
Nafrialdi
N
N
Ribstein
J
J
Mimran
A
A
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000032:analysis; D005110:Extracellular Space / Q000187:drug effects*; D006400:Hematocrit; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology
D001798:Blood Proteins; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D009529:Nicardipine