TY - JOUR
T1 - Endogenous angiotensin II but not atrial natriuretic peptide modulates the effect of nicardipine on extracellular fluid partition in the rat
AU - Valentin, Jean Pierre
AU - Nafrialdi, null
AU - Ribstein, Jean
AU - Mimran, Albert
PY - 1993/9
Y1 - 1993/9
N2 - 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 µg/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 losarían 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.
AB - 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 µg/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 losarían 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.
KW - Angiotensin converting enzyme inhibition
KW - Angiotensin receptor blockade
KW - Atrial natriuretic peptide
KW - Monoclonal anti-atrial natriuretic peptide antibodies
KW - Vascular permeability
UR - http://www.scopus.com/inward/record.url?scp=0027184622&partnerID=8YFLogxK
U2 - 10.1097/00004872-199309000-00010
DO - 10.1097/00004872-199309000-00010
M3 - Article
C2 - 8254178
AN - SCOPUS:0027184622
SN - 0263-6352
VL - 11
SP - 961
EP - 967
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 9
ER -