Natriuretic activity of amlodipine, diltiazem, and nitrendipine in saline-loaded anesthetized dogs.
The natriuretic effects of amlodipine, diltiazem, and nitrendipine were compared in anesthetized dogs receiving a continuous saline load. Doses of all agents were selected that caused similar degrees of coronary vasodilation (approximately 50% of maximum) but that had only minimal peripheral vasodilator effect. Bolus doses of either saline, amlodipine, or diltiazem were administered intravenously. Because of its short duration of action, nitrendipine was given by infusion for 2 h and its effects were compared with infused vehicle [5% polyethylene glycol (PEG 300)]. Bolus amolodipine (105 micrograms/kg) and infused nitrendipine (1 micrograms/kg/min) had a similar hemodynamic profile of action: Both drugs caused a sustained reduction of coronary vascular resistance (CVR) (131.1 to 77.9 and 124.9 to 76.7 dyn/s/cm-5 at 2 h, respectively), but only slightly reduced systemic vascular resistance, with no significant change in blood pressure. Diltiazem (150 micrograms/kg) caused an initial transient reduction of CVR (141.9 to 77.0), followed by a secondary, more sustained action (100.1 at 180 min). Cumulative sodium excretion, measured 1 h after saline, amlodipine, and diltiazem, was 1.96, 5.11, and 5.74 mEq, respectively, increasing to 4.05, 13.19 (p less than 0.05), and 13.09 (p less than 0.05) at 2 h. Significant increases were maintained for up to 3.5 h. A similar pattern was observed with urine volume. Cumulative sodium excretion was 10.05 and 8.27 mEq for vehicle and nitrendipine, respectively, at the end of the 2-h infusion (NS), increasing to 15.88 and 13.73 mEq 60 min later (NS). Nitrendipine did not increase urine volume in comparison with its vehicle alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Carter
A J
AJ
Pfizer Central Research, Sandwich, Kent, England.
Gardiner
D G
DG
Burges
R A
RA
D017311:Amlodipine; D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D009318:Natriuresis / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D012964:Sodium / Q000652:urine; D013997:Time Factors
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009568:Nitrendipine; D012964:Sodium; D004110:Diltiazem; D009543:Nifedipine