Antiadrenergic effect of M-cholinoceptor stimulation on human ventricular contractility in vivo.
The relevance of an indirect negative inotropic effect of pharmacological or vagally mediated M-cholinoceptor stimulation in the human ventricle in vivo is unknown. The inotropic response induced by isoproterenol (isoprenaline, 20 ng.kg-1 x min-1), measured by m-mode echocardiography as the increase of fractional shortening in seven healthy subjects, was reduced from 17.1 +/- 4.3 to 9.1 +/- 3.9% (P < 0.01) by M-cholinoceptor stimulation using intravenous injection of 3.6 micrograms/kg carbachol. However, the inotropic response of increasing doses of isoprenaline (5-20 ng.kg-1 x min-1) did not differ in 13 healthy subjects without and after M-cholinoceptor blockade (atropine, 0.015 mg/kg i.v.); the increase of fractional shortening amounted to 17.4 +/- 4.0 vs. 19.5 +/- 4.8% (NS) in response to 20 ng.kg-1 x min-1 isoprenaline. It is concluded that pharmacological M-cholinoceptor stimulation of the human ventricle significantly reduces the inotropic response of beta-adrenoceptor stimulation. This may offer a new therapeutic approach to attenuate an increased cardiac sympathetic tone. However, M-cholinoceptor blockade, i.e., interruption of parasympathetic influences, does not augment the inotropic response to beta-adrenoceptor stimulation. Therefore, in healthy resting humans a physiological role of the parasympathetic nervous system in mediating an indirect negative inotropic effect on ventricular contractility seems to be absent.
Von Scheidt
W
W
Medizinische Klinik I, Klinikum Grosshadern, Universität München, Germany.
Böhm
M
M
Stäblein
A
A
Autenrieth
G
G
Erdmann
E
E
D000328:Adult; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018680:Cholinergic Antagonists; D004452:Echocardiography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000502:physiology*; D016276:Ventricular Function / Q000187:drug effects
D018680:Cholinergic Antagonists; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D001285:Atropine; D002217:Carbachol; D007545:Isoproterenol