Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis

Citation
M. Honda et al., Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis, CLIN SCI, 101(4), 2001, pp. 421-427
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research General Topics
Journal title
CLINICAL SCIENCE
ISSN journal
0143-5221 → ACNP
Volume
101
Issue
4
Year of publication
2001
Pages
421 - 427
Database
ISI
SICI code
0143-5221(200110)101:4<421:DNAOCC>2.0.ZU;2-I
Abstract
This study examined the effects of different types of calcium channel antag onists on renal haemodynamics and natriuresis. The intravenous infusion of nifedipine (L-type blocker), efonidipine (L/T-type blocker) or mibefradil ( predominant T-type blocker) into anaesthetized dogs elicited similar, albei t modest, reductions in blood pressure. Nifedipine(1 mug(.)min(-1.)kg(-1)) increased renal plasma flow (RPF) (23 +/- 6%; P < 0.05) and glomerular filt ration rate (GFR) (25 +/- 5%; P < 0.05) (all values are means +/- S.E.M., n = 7). Efonidipine (0.33 mug(.)min(-1.)kg(-1)) also elevated RPF (18 +/- 6% ; P < 0.05), and tended to increase GFR (17 +/- 8%; P = 0.08). These antago nists exerted contrasting actions on the filtration fraction (FF), with an increase being elicited by nifedipine, whereas efonidipine had no effect. F urthermore, mibefradil (0.01-1 mug(.)min(-1.)kg(-1)) slightly elevated RPF (between 5 +/- 3% and 8 +/- 3%), but failed to alter GFR, resulting in a de crease in FF. Nifedipine slightly increased urinary sodium excretion (UNaV) (29 +/- 16% increase at 1 mug(.)min(-1.)kg(-1)) and fractional sodium excr etion (FENa) (18 +/- 14%), whereas efonidipine (0.33 mug(.)min(-1.)kg(-1)) elicited marked elevations in UNaV (110 +/- 38%; P < 0.05) and FENa (102 +/ - 44%; P < 0.05). Mibefradil (1 mug(.)min(-1.)kg(-1)) exerted a moderate na triuretic action [UNaV, +60 +/- 32% (P = 0.1); FENa, +67 +/- 20% (P < 0.05) ]. Furthermore, although a positive correlation was observed between UNaV a nd urinary nitrate/nitrite excretion, no differences were noted between the various calcium channel antagonists. Collectively, this study demonstrates that the glomerular haemodynamic and natriuretic actions of these calcium channel antagonists, which possess diverse blocking activities on L/T-type channels, vary, Based on the divergent actions on FF (i.e. increase, no cha nge and decrease by nifedipine, efonidipine and mibefradil respectively), t he natriuretic action of calcium channel antagonists is possibly attributed to the inhibition of tubular sodium reabsorption associated with increased post-glomerular blood flow, rather than increased GFR.