Divergent natriuretic action of calcium channel antagonists in mongrel dogs

Renal haemodynamics as a determinant of natriuresis

M. Honda, K. Hayashi, H. Matsuda, E. Kubota, Hirobumi 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

Fingerprint

Natriuresis
Mibefradil
Calcium Channel Blockers
Nifedipine
Renal Plasma Flow
Glomerular Filtration Rate
Hemodynamics
Dogs
Kidney
Sodium
Nitrites
Intravenous Infusions
Nitrates
efonidipine
Blood Pressure

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Divergent natriuretic action of calcium channel antagonists in mongrel dogs : Renal haemodynamics as a determinant of natriuresis. / Honda, M.; Hayashi, K.; Matsuda, H.; Kubota, E.; Tokuyama, Hirobumi; Okubo, K.; Ozawa, Y.; Saruta, T.

In: Clinical Science, Vol. 101, No. 4, 2001, p. 421-427.

Research output: Contribution to journalArticle

Honda, M. ; Hayashi, K. ; Matsuda, H. ; Kubota, E. ; Tokuyama, Hirobumi ; Okubo, K. ; Ozawa, Y. ; Saruta, T. / Divergent natriuretic action of calcium channel antagonists in mongrel dogs : Renal haemodynamics as a determinant of natriuresis. In: Clinical Science. 2001 ; Vol. 101, No. 4. pp. 421-427.
@article{c99f2ed560084abf892bb1f52b25fe09,
title = "Divergent natriuretic action of calcium channel antagonists in mongrel dogs: Renal haemodynamics as a determinant of natriuresis",
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.",
keywords = "Efonidipine, Filration fraction, Mibefradil, Nifedipine, Renal haemodynamics",
author = "M. Honda and K. Hayashi and H. Matsuda and E. Kubota and Hirobumi Tokuyama and K. Okubo and Y. Ozawa and T. Saruta",
year = "2001",
doi = "10.1042/CS20010056",
language = "English",
volume = "101",
pages = "421--427",
journal = "Clinical Science",
issn = "0143-5221",
publisher = "Portland Press Ltd.",
number = "4",

}

TY - JOUR

T1 - Divergent natriuretic action of calcium channel antagonists in mongrel dogs

T2 - Renal haemodynamics as a determinant of natriuresis

AU - Honda, M.

AU - Hayashi, K.

AU - Matsuda, H.

AU - Kubota, E.

AU - Tokuyama, Hirobumi

AU - Okubo, K.

AU - Ozawa, Y.

AU - Saruta, T.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Efonidipine

KW - Filration fraction

KW - Mibefradil

KW - Nifedipine

KW - Renal haemodynamics

UR - http://www.scopus.com/inward/record.url?scp=0034815592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034815592&partnerID=8YFLogxK

U2 - 10.1042/CS20010056

DO - 10.1042/CS20010056

M3 - Article

VL - 101

SP - 421

EP - 427

JO - Clinical Science

JF - Clinical Science

SN - 0143-5221

IS - 4

ER -