Cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide in the anaesthetised rat and isolated right atria.
The cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide (DDA) from Andrographis paniculata (Burm.f.) Nees (Acanthaceae) was elucidated in anaesthetised Sprague-Dawley (SD) rats and isolated rat right atria. In anaesthetised rats, DDA produced significant falls in mean arterial blood pressure (MAP) and heart rate in a dose-dependent manner with the maximum decrease of 37.6 +/- 2.6% and 18.1 +/- 4.8%, respectively. The ED50 value for MAP was 3.43 mmol kg-1. Pharmacological antagonist studies were done using this dose. The hypotensive action of DDA was not mediated through effects on the alpha-adrenoceptor, muscarinic cholinergic and histaminergic receptors, for it was not affected by phentolamine, atropine as well as pyrilamine and cimetidine. However, it seems to work via adrenoceptors, autonomic ganglia receptor and angiotensin-converting enzyme, since the hypotensive effect of DDA was negated or attenuated in the presence of propranolol, hexamethonium and captopril. In the isolated right atria, DDA caused negative chronotropic action and antagonised isoproterenol-induced positive chronotropic actions in a non-competitive and dose-dependent manner. These results further supported the bradycardia-inducing and beta-adrenoceptor antagonistic properties of DDA in vivo.
Zhang
C
C
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Japan.
Kuroyangi
M
M
Tan
B K
BK
D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D003634:DDT / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology