5-Hydroxytryptamine-induced increase in left ventricular dP/dtmax does not suggest the presence of ventricular 5-HT4 receptors in the pig.
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 micrograms.kg-1), and the beta-adrenoceptor agonist, isoprenaline (0.01, 0.03 and 0.1 micrograms.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 micrograms.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 micrograms.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.(ABSTRACT TRUNCATED AT 250 WORDS)
Saxena
P R
PR
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Villalón
C M
CM
Dhasmana
K M
KM
Verdouw
P D
PD
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine
D002316:Cardiotonic Agents; D011985:Receptors, Serotonin; D012701:Serotonin