Cardiovascular pharmacology of vasodilating drugs in the pig : a study on dihydropyridine calcium-channel blockers, pyridazinone-derivatives and nicorandil
In this thesis the cardiovascular pharmacological actions of a number of
vasodilating drugs have been studied and compared in pigs. Firstly, we
compared the vasodilator profile of the dihydropyridine-derivatives
nisoldipine, nimodipine and nifedipine and also studied the claimed preference
of nisoldipine for the coronary circulation (Kazda et al., 1980; Serruys et al.,
1985; Drexler et al., 1986b) and of nimodipine for the cerebral circulation
(Kazda et al., 1982) (chapters 2-5). Secondly, since the perfusion of organs
and tissues may be compromised in several pathological disorders for which
vasodilating drugs might be employed (ischemic heart disease, heart failure,
hypertension), we compared the vasodilator profiles of the dihydropyridinederivatives
nisoldipine and nimodipine with those of pimobendan, UD-CG 212
CL and nicorandil after intravenous administration in anesthetized pigs
(chapters 6-9). Thirdly, in view of the potentially useful combination of
vasodilators and 13-adrenoceptor antagonists to reduce h;,rpotension -induced
baroreceptor reflex-mediated tachycardia, we compared the systemic
hemodynamic actions of the different vasodilating drugs in conscious pigs in
the absence or presence of 13-adrenoceptor blockade (chapters 9-11). Finally,
the long-held view that vasodilation in ischemic myocardium is maximal (see Berne and Rubio, 1979) and, therefore, vasodilators may induce coronary
"steal" (Weintraub et al., 1981; Gross and Warltier, 1981; Gewirtz et al., 1984),
may not hold true. Recently, vasodilator therapy has been shown to induce
an improvement of perfusion and function of ischemic myocardial areas by
recruiting vasodilator reserve (Gorman. et al., 1984; Heusch and Deussen, 1984;
Aversano and Becker, 1985; Canty and Klocke, 1985; Pantely et al., 1985). In
view of these new findings, lending support to the possible usefulness of
vasodilator drugs in myocardial ischemia, we investigated the effects of
nisoldipine on perfusion of myocardium distal to a fixed concentric coronary
artery stenosis in conscious pigs (chapter 12). In. addition, the possible
anti-ischemic action of this drug was studied during myocardial ischemiainduced
in animals subjected to treadmill-exercise (chapter 13)