The influence of experimental hyperlipidemia on the time course of contractility during simulated ischaemia and reperfusion and responsiveness to phenylephrine of rat heart papillary muscle.
The aim of this study was to examine the influence of simulated ischaemia on the contractility and responsiveness to phenylephrine of rat isolated papillary muscle in standard diet fed (SD) and hyperlipidemic diet fed (HLD) rats. The following parameters were measured: force of contraction (Fc), rate of rise (+dF/dt) and rate of fall (-dF/dt) of force of contraction, time to peak contraction (ttp) and relaxation time at 10% of total amplitude of contraction (tt10). The baseline values of Fc and +dF/dt, but, not -dF/dt, were significantly lower in HLD group than in SD group. Tissues from HLD rats were more sensitive to ischaemia regarding Fc, +dF/dt and -dF/dt. Moreover, reprefusion completely reversed the effects of ischaemia only in SD rats, but not in HLD rats, regarding Fc and +dF/dt. In contrast, a recovery of -dF/dt during reperfusion occurred only in the HLD group. In SD rats, phenylephrine (10 and 30 microM) had no effect on the contractility or induced megative inotropic effects (100 and 300 microM). Propranolol (1 microM), a non-selective blocker of beta-adrenoceptors, had no effects on this action. Chloroethylclonidine (CEC) (1 microM), a selectivw blocker of alpha 1b-adrenoceptor subtype, but not WB-4101(2-((2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane), a selective blocker of alpha 1a adrenoceptor subtype, abolishes the negative inotropic action of phenylephrine. In HLD rats, phenylephrine had positive inotropic action (10 and 30 microM). The results indicate that hyperlipidemic diet in rats leads to the suppression of force of contraction and velocity of contraction, but not velocity of relaxation of isolated heart muscle. Under such a condition, heart muscle is more sensitive to ischaemia, but has better responsiveness to phenylephrine after ischeamia-reperfusion period.
Kocić
I
I
Department of Pharmacology, Medical University of Gdańsk, Poland. ikocic@amg.gda.pl
Dworakowska
D
D
Konstański
Z
Z
Dworakowski
R
R
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D005260:Female; D006949:Hyperlipidemias / Q000150:complications / Q000178:diet therapy* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D010210:Papillary Muscles / Q000187:drug effects* / Q000503:physiopathology; D010656:Phenylephrine / Q000627:therapeutic use*; D051381:Rats; D014280:Triglycerides / Q000097:blood
D000316:Adrenergic alpha-Agonists; D002316:Cardiotonic Agents; D014280:Triglycerides; D010656:Phenylephrine; D002784:Cholesterol