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

M. Honda, Koichi Hayashi, H. Matsuda, E. Kubota, H. Tokuyama, K. Okubo, Y. Ozawa, T. Saruta

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

This study examined the effects of different types of calcium channel antagonists on renal haernodynarnics 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, albeit modest, reductions in blood pressure. Nifedipine (I μg·min-1·kg-1) increased renal plasma flow (RPF) (23±6%; P<0.05) and glomerular filtration rate (GFR) (25±5%; P < 0.05) (all values are means±S.E.M., n=7). Efonidipine (0.33 μg·min-1·kg-1) also elevated RPF (18±6%; P<0.05), and tended to increase GFR (17±8%; P=0.08). These antagonists exerted contrasting actions on the filtration fraction (FF), with an increase being elicited by nifedipine, whereas efonidipine had no effect. Furthermore, mibefradil (0.01-1 μg·min-1·kg-1) slightly elevated RPF (between 5±3% and 8±3%), but failed to alter GFR, resulting in a decrease in FF. Nifedipine slightly increased urinary sodium excretion (UNaV) (29±16% increase at I μg·min-1·kg-1) and fractional sodium excretion (FENa) (18±14%), whereas efonidipine (0.33μg·min-1·kg-1) elicited marked elevations in UNaV (110±38%; P<0.05) and FENa (102±44%; P<0.05). Mibefradil (I μg·min-1·kg-1) exerted a moderate natriuretic action [UNaV, +60±32% (P=0.1); FENa, +67±20% (P<0.05)]. Furthermore, although a positive correlation was observed between UNaV and urinary nitrate/nitrite excretion, no differences were noted between the various calcium channel antagonists. Collectively, this study demonstrates that the glomerular haernodynamic 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 change and decrease by nifedipine, efonidipine and mibefradil respectively), the 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.

Original languageEnglish
Pages (from-to)421-427
Number of pages7
JournalClinical Science
Volume101
Issue number4
DOIs
Publication statusPublished - 2001 Oct 16

Keywords

  • Efonidipine
  • Filration fraction
  • Mibefradil
  • Nifedipine
  • Renal haemodynamics

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Divergent natriuretic action of calcium channel antagonists in mongrel dogs: Renal haemodynamics as a determinant of natriuresis'. Together they form a unique fingerprint.

  • Cite this