Effects of dilevalol on human atrial muscle.
The beta 1- and beta 2-adrenoceptor agonist effects of dilevalol on human heart tissue were studied in vitro. The receptors were studied independently of one another through the use of selective antagonists. Human right atrial appendages were generally cut into four strips which were then set up in parallel in an organ bath system. All tissues were incubated either with 300 nM CGP 20712A to block beta 1-adrenoceptors, or with 50 nM ICI 118551, to block beta 2-adrenoceptors. Alpha-adrenoceptors and tissue uptake of catecholamines were blocked using 5 microM phenoxybenzamine. The atrial strips from one patient were then exposed either to vehicle or to cumulative additions of dilevalol, (+)- pindolol or salbutamol (10(-8) to 10(-5) M) and the resulting force of contraction was expressed as a percentage of the inotropic response obtained with a saturating dose of (-)-isoprenaline. The beta-antagonist effects of the three substances were also studied, by running a dose-response curve to noradrenaline or adrenaline as appropriate following the addition of the substance of interest. Neither dilevalol nor (+)-pindolol had any intrinsic sympathomimetic activity at the atrial beta 1- or beta 2-adrenoceptors. Both dilevalol and (+)-pindolol caused marked antagonism of the atrial beta-adrenoceptors. They caused similar blockade of the beta 2-adrenoceptors but not of the beta 1-adrenoceptors.
Brown
M J
MJ
Department of Medicine, University of Cambridge, UK.
Sanders
L
L
D000420:Albuterol / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007741:Labetalol / Q000494:pharmacology*; D008722:Methods; D010869:Pindolol / Q000494:pharmacology
D010869:Pindolol; D000420:Albuterol; D007741:Labetalol