caa a22 4500 46907793X CHVBK 20180323132940.0 cr unu---uuuuu 170328e19921201xx s 000 0 eng 10.1007/BF00168735 doi (NATIONALLICENCE)springer-10.1007/BF00168735 5-Hydroxytryptamine-induced increase in left ventricular dP/dtmax does not suggest the presence of ventricular 5-HT4 receptors in the pig [Elektronische Daten] [Pramod Saxena, Carlos Villalón, K. Dhasmana, Pieter Verdouw] Summary: Although 5-hydroxytryptamine (5-HT) increases porcine atrial force and rate via 5-HT4 receptors, its effect on left ventricular contractility is not known. Therefore, using the maximum rate of rise of left ventricular pressure (LVdP/dtmax) as an index of cardiac contractility, we have attempted to analyze the possible role of ventricular 5-HT4 receptors in the anaesthetized pig. The full agonists at 5-HT4 receptors, 5-HT and 5-methoxytryptamine (each 3, 10 and 30 μg · kg−1), and the β-adrenoceptor agonist, isoprenaline (0.01, 0.03 and 0.1 μg · kg−1), increased heart rate, LVdP/dtmax and cardiac output. For a given degree of tachycardia, the increase in LVdP/dtmax by isoprenaline was substantially more than that observed with either 5-HT or 5-methoxytryptamine. The 5-HT4 receptor partial agonist, renzapride (3, 10, 30, 100 and 300 μg · kg−1), also increased heart rate and LVdP/dtmax dose-dependently. When the heart was paced at 150 beats · min−1, increases in LVdP/dtmax as well as cardiac output (except with the highest doses) by 5-HT, 5-methoxytryptamine and isoprenaline were clearly attenuated. However, the magnitude of attenuation of LVdP/dtmax responses by cardiac pacing was more marked in the case of 5-HT and 5-methoxytryptamine than with isoprenaline. The effects of renzapride (300 μg · kg−1) and tropisetron (0.3 and 3 mg · kg−1) on increases in heart rate and LVdP/dtmax by 5-HT, 5-methoxytryptamine and isoprenaline were also studied. In the absence of atrial pacing, both renzapride and tropisetron (3 mg · kg−1) effectively antagonized the responses to 5-HT and 5-methoxytryptamine; except for some decrease in the LVdP/dtmax response by tropisetron, the effect of isoprenaline remained essentially unchanged after the antagonists. During atrial pacing, renzapride significantly antagonized the responses to the first two doses of 5-HT, but the responses to the highest 5-HT dose and to 5-methoxytryptamine remained unaffected. Though, particularly after its higher dose, tropisetron reduced the responses to 5-HT and 5-methoxytryptamine, isoprenaline responses were also affected. The above results show that a significant part of the increase in LVdP/dtmax by 5-HT receptor agonists in the anaesthetized pig is a consequence of tachycardia elicited by these compounds via 5-HT4 receptors. Since the increase in LVdP/dtmax, compared to tachycardia, was much less with 5-HT and 5-methoxytryptamine than with isoprenaline, and since the antagonism by renzapride and tropisetron against 5-HT and 5-methoxytryptamine during atrial pacing was relatively weaker and/or unspecific, it appears unlikely that the increase in LVdP/dtmax, during atria] pacing is mediated by ventricular 5-HT4 receptors. This view is substantiated by our recent in vitro experiments where 5-HT (0.01 to 100 μmol/l) failed to significantly increase contractions of porcine left ventricular trabeculae. Springer-Verlag, 1992 5-HT4 receptors nationallicence 5-Hydroxytryptamine nationallicence 5-Hydroxytryptamine receptors nationallicence Inotropic effect nationallicence Left ventricle nationallicence Pig nationallicence Renzapride nationallicence Tropisetron nationallicence Saxena Pramod Department of Pharmacology, Cardiovascular Research Institute "COEUR”, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P. O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands aut Villalón Carlos Department of Pharmacology, Cardiovascular Research Institute "COEUR”, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P. O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands aut Dhasmana K. Anesthesiology, The Netherlands aut Verdouw Pieter Laboratory of Experimental Cariology (Thorax Centre), Cardiovascular Research Institute "COEUR”, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P. O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/6(1992-12-01), 629-636 0028-1298 346:6<629 1992 346 210 https://doi.org/10.1007/BF00168735 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168735 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Saxena Pramod Department of Pharmacology, Cardiovascular Research Institute "COEUR”, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P. O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Villalón Carlos Department of Pharmacology, Cardiovascular Research Institute "COEUR”, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P. O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Dhasmana K. Anesthesiology, The Netherlands aut NATIONALLICENCE 700 1- Verdouw Pieter Laboratory of Experimental Cariology (Thorax Centre), Cardiovascular Research Institute "COEUR”, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P. O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/6(1992-12-01), 629-636 0028-1298 346:6<629 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer