Properties of the inotropic response in rat papillary muscles to the dihydropyridine "Ca-channel activator" BAY K 8644.
The aim of the present study was 1) to characterize qualitatively the positive inotropic effect of the Ca-channel activator BAY K 8644 and to compare this response to response-types with known and different relationship to the cyclic AMP (cAMP) system (e.g. responses elicited through alpha- and beta-adrenergic receptor stimulation) and 2) to study the effect of simultaneous muscarinic cholinergic stimulation upon the BAY K 8644 response in order to further evaluate the role of the cAMP system in this response. The responses were evaluated in isolated, electrically paced, isometrically contracting papillary muscles from rat heart. Isometric tension (Tmax), rate of rise and decline of tension (first derivative = T') and rate of transition from tension rise to tension decline (negative part of second derivative = T") were recorded. In the presence of the alpha 1-adrenergic receptor blocker prazosin (10(-7) mol/l) and the beta-adrenergic receptor blocker timolol (10(-6) mol/l), the positive inotropic effect of 1.7 x 10(-6) mol/l BAY K 8644 developed rather slowly with a time to half maximal effect of about 4 minutes. Qualitatively the response was characterized by an almost proportional ("symmetrical") increase in all parts of the contraction-relaxation cycle with a small prolongation of time to peak tension and of the duration of the whole cycle. This response contrasted sharply with the cAMP-dependent response to beta-receptor stimulation (beta-type response with shortening of time to peak tension), but was very similar to the cAMP-independent response to alpha-receptor stimulation (alpha-type response).(ABSTRACT TRUNCATED AT 250 WORDS)
Skomedal
T
T
Department of Pharmacology, University of Oslo, Norway.
Schiander
I
I
Aass
H
H
Osnes
J B
JB
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013999:Timolol / Q000494:pharmacology
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D013999:Timolol; D002217:Carbachol; D000242:Cyclic AMP; D011224:Prazosin