COMPARISON OF THE NEGATIVE INOTROPIC EFFE CTS OF NIFEDIPINE AND NISOLDIPINE USING ISOVOLUMIC CONTRACTILITY PARAMETERS IN THE RAT

The vasoselectivity of new dihydropyridine calcium antagonists is much higher as compared to their prototype substance nifedipine. To invest igate whether an equihypotensive dose of a new dihydropyridine has les s 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 pre ssure (LVPiso) and the maximal isovolumic rate of change of LV-pressur e (dp/dt(max)iso) were determined to achieve load independent paramete rs of LV contractility. To evaluate the effect of the infused volume, the stability of the preparation and the hemodynamic effects of the dr ug-solvent, two groups with either infusion of isotonic NaCl-solution or 20% ethanol sewed as controls. NIF and NIS were infused in three eq uihypotensive doses within 7 min (NIF 250, 500, 1000 mu g/kg; NIS 12.5 , 25, 50 mu g/kg). The decrease of the peripheral resistance for these doses was 74 +/- 6, 67 +/- 6, and 58 +/- 7% for NIF, and 78 +/- 7, 65 +/- 8, and 56 +/- 7% for NIS (p < 0.0001 for all groups). In the cont rol groups the afterload remained unchanged. NIF-infusion resulted in a dose-dependent decrease of LVPiso at the end of the infusion period (in per cent 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/dt(max)iso 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 cont ractility parameters decreased slightly after the higher dosage (25 mu g/kg) at the end of the infusion period only (LVPiso 96 +/- 3%, p < 0 .01; dp/dt(max)iso 93 +/- 5%, p < 0.01). There was no depressive effec t 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.