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Studies on the eleterious effects of free radicals on myocardial contractility and hemodynamics in dogs: Protection by felodipine, a dihydropyridine calcium antagonist
Author(s) -
Chintala Madhu S.,
Jacinto Severina M.,
Jandhyala Bhagavan S.
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430270308
Subject(s) - felodipine , contractility , dihydropyridine , calcium , medicine , nicardipine , xanthine oxidase , chemistry , antagonist , hemodynamics , blood pressure , cardiology , anesthesia , receptor , biochemistry , enzyme
Abstract There is convincing evidence that re‐oxygenation of ischemic organs is associated with the formation of oxygen free radicals and increases in cell calcium that exacerbate the ischemic injury. The objective of the present studies was to determine whether felodipine, a dihydropyridine calcium antagonist, would be effective in preventing cardiovascular toxicity produced by oxygen free radicals. In pentobarbital‐anesthetized dogs, intravenous (i.v.) administration of xanthine plus xanthine oxidase [X + XO] resulted in a rapid fall in arterial blood pressure (by 50–60 mmHg) and heart rate (by 30–40 beats/min). All the indices reflecting cardiac function such as contractility index (max dp/dt/p), cardiac output, stroke volume, left ventricular stroke work, and left ventricular minute work were significantly attenuated during a 120 min observation period. Pretreatment of the animals with felodipine (0.01 μmol/kg, i.v.) provided moderate but significant protection from [X + XO]‐induced deterioration of cardiovascular function, whereas the higher dose (0.05 μmol/kg, i.v.) effectively prevented any adverse alterations in cardiovascular function. The results obtained in the present studies suggest that oxygen free radicals facilitate calcium overload in the ischemic cells and can account for the efficacy of several calcium channel antagonists in preventing ischemic injury such as ischemic renal failure in various experimental models. © 1992 Wiley‐Liss, Inc.