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 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 (1 microgram.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 microgram .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 microgram.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 (U(Na)V) (29+/-16% increase at 1 microgram .min(-1).kg(-1)) and fractional sodium excretion (FE(Na)) (18+/-14%), whereas efonidipine (0.33 microgram .min(-1).kg(-1)) elicited marked elevations in U(Na)V (110+/-38%; P<0.05) and FE(Na) (102+/-44%; P<0.05). Mibefradil (1 microgram .min(-1).kg(-1)) exerted a moderate natriuretic action [U(Na)V, +60+/-32% (P=0.1); FE(Na), +67+/-20% (P<0.05)]. Furthermore, although a positive correlation was observed between U(Na)V 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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.forename: E
authors.initials: E
authors.lastname: Kubota
authors.forename: H
authors.initials: H
authors.lastname: Tokuyama
authors.forename: K
authors.initials: K
authors.lastname: Okubo
authors.forename: Y
authors.initials: Y
authors.lastname: Ozawa
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020747:Calcium Channels, T-Type / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000652:urine; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011453:Prostaglandins / Q000652:urine; D012079:Renal Circulation / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D011453:Prostaglandins; D020748:Mibefradil; D009569:Nitric Oxide; C066425:efonidipine; D009543:Nifedipine