Effects of a new calcium antagonist, Rec 15/2375, on cardiac contractility of conscious rabbits.
The new calcium antagonist Rec 15/2375, supposed to be selective for the vascular tissue, was compared to nifedipine, a non-selective agent that reduces blood pressure and impairs cardiac inotropism as well. Six rabbits, chronically catheterized and continuously monitored for systemic blood pressure, heart rate and the isovolumic contractility index dP/Tmax, were alternatively treated with Rec 15/2375 and nifedipine, according to a randomized cross-over design. Both drugs were given under either autonomically intact (AI) or suppressed (AS) heart function control, induced by cholinergic and beta-adrenoceptor blockade. The two agents reduced mean arterial blood pressure comparably and dose-dependently (P less than 0.01) under both experimental conditions (from 10 to 40%), thus causing heart rate to increase reflexly (P less than 0.01), similarly between drugs in AI rabbits, whereas the AS manoeuvre totally abolished such a response. Cardiac contractility, on the other hand, displayed opposing behaviour between the two drugs. Rec 15/2375 caused mild but significant (P less than 0.01) increases, which were similar at all doses (+10, +15%) and insensitive to the AS intervention, whereas nifedipine caused dose-dependent reductions (from -10 to -60%; P less than 0.01) of comparable intensity as mean blood pressure decrease in both protocols. We conclude that Rec 15/2375 effectively lowers blood pressure with no impairment, unlike nifedipine, of cardiac inotropism and we discuss the possibility that dP/dTmax may be increased as a result of the haemodynamic rearrangement following after-load reduction.
Bianchi
G
G
Department of Pharmacology, Milano, Italy.
Passoni
A
A
Griffini
P L
PL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010042:Ouabain; D009543:Nifedipine; C060343:lercanidipine