This study examined the effects of different types of calcium channel antagonists 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, albeit modest, reductions in blood pressure. Nifedipine (1μgċmin-1ċkg-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 (0.33μgċmin-1ċkg-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 (0.01-1μgċmin-1ċkg-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 1μgċmin-1ċkg-1) and fractional sodium excretion (FENa) (18±14%), whereas efonidipine (0.33μgċmin-1ċkg-1) elicited marked elevations in UNaV (110±38%; P<0.05) and FENa (102±44%; P<0.05). Mibefradil (1μgċmin-1ċkg-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 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 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.
Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis
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Masanori HONDA, Koichi HAYASHI, Hiroto MATSUDA, Eiji KUBOTA, Hirobumi TOKUYAMA, Ken OKUBO, Yuri OZAWA, Takao SARUTA; Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis. Clin Sci (Lond) 1 October 2001; 101 (4): 421–427. doi: https://doi.org/10.1042/cs1010421
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