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).