[Comparison of the negative inotropic properties of nifedipine and nisoldipine using isovolumetric contractile parameters of the rat in vivo].
The vasoselectivity of new dihydropyridine calcium antagonists is much higher as compared to their prototype substance nifedipine. To investigate whether an equihypotensive dose of a new dihydropyridine has less negative inotropic properties in an intact circulation, nifedipine (NIF) and nisoldipine (NIS) were infused intravenously in an open-chest, anaesthetized rat model. The maximal isovolumic left ventricular pressure (LVPiso) and the maximal isovolumic rate of change of LV-pressure (dp/dtmaxiso) were determined to achieve load independent parameters of LV contractility. To evaluate the effect of the infused volume, the stability of the preparation and the hemodynamic effects of the drug-solvent, two groups with either infusion of isotonic NaCl-solution or 20% ethanol served as controls. NIF and NIS were infused in three equihypotensive doses within 7 min (NIF 250, 500, 1000 micrograms/kg; NIS 12.5, 25, 50 micrograms/kg). The decrease of the peripheral resistance of these doses was 74 +/- 6, 67 +/- 6, and 58 +/- 7% for NIF, and 78 +/- 7, 65 +/- 8, and 56 +/- 7% for NIS (p < 0.001 for all groups). In the control groups the afterload remained unchanged. NIF-infusion resulted in a dose-dependent decrease of LVPiso at the end of the infusion period (in percent of controls: NIF250 88 +/- 3%, p < 0.001; NIF500 74 +/- 3%, p < 0.001) as well as 15 min after the end of the infusion. In the same way dp/dtmaxiso decreased significantly after NIF at the end of infusion (NIF 250 82 +/- 6%, p < 0.001; NIF500 61 +/- 8%, p < 0.001) and 15 min after the end of the infusion. After NIS-infusion the contractility parameters decreased slightly after the higher dosage (25 micrograms/kg) at the end of the infusion period only (LVPiso 96 +/- 3%, p < 0.01; dp/dtmaxiso 93 +/- 5%, p < 0.01). There was no depressive effect on the isovolumic contractility parameters at the end of infusion of the lower dosage and 15 min after the drug-infusion of all dosages of NIS. Therefore, nisoldipine, as an example of a new dihydropyridine, has significantly less negative inotropic properties over a wide range of doses as compared to nifedipine in equihypotensive doses.
Mauser
M
M
Medizinische Klinik, Abteilung III der Universität Tübingen.
Hoffmeister
H M
HM
Beyer
M
M
Seipel
L
L
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D015737:Nisoldipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D015737:Nisoldipine; D009543:Nifedipine
Vergleich der negativ inotropen Eigenschaften von Nifedipin und Nisoldipin unter Verwendung isovolumetrischer Kontraktilitätsparameter bei der Ratte in vivo.