Relations Of Cardiac Dopamine D₁-receptors To The Development Of Myocardial Hypertrophy In Rats

Aim The role of myocardial dopamine-D1 receptors are yet to be clarified.The aim of this study is to examine the relations of cardiac dopamine D1-receptors to the development of myocardial hypertrophy. Therefore, in thepresent experiment, we studied the effects of fenoldopam (FODA), a specificdopamine D1-receptor agonist and SCH23390, a specific dopamine D1-receptorantagonist on the formation of myocardial hypertrophy in rats in the presence ofβ-receptor blockade. The alterations in the responsiveness of cardiac dopamineD1-receptors were also examined in rats when myocardial hypertrophy hasestablished. Methods The myocardial hypertrophy model was established by ligatingthe abdominal aorta. Thirty Wistar healthy male rats were randomly divided intofive groups: aorta constriction group (group A); normal control group (group C);aorta constriction + betaloc group (group A+B); aorta constriction + betaloc +SCH23390 group (group A+B+S); normal rats + betaloc + FODA group (groupB+F). Cardiac function and heart weight indices were determined for all groupsat 4 weeks after treatment. In addition, the production of cAMP induced byFODA stimulation in hypertrophied myocardium (group A) was also examined. Results (1) As compared with control group, in group A the cardiacfunction indices were significantly reinforced, the heart weight indicesincreased remarkably and the cross section area of cardiac myocyte augmentedat 4 weeks after abdominal aortic constriction. This indicates that the myocardialhypertrophy model was successfully established. (2) There were no significantdifferences for all parameters between group A+B and group A indicating that IIIthe formation of hypertrophy was basically not affected by blockading β-receptors. (3) In group A+B+S, the changes in heart weight indices and the crosssection area of cardiac myocyte were all significantly attenuated as comparedwith group A or group A+B (p<0.05). This indicates that blockade of cardiacdopamine D1-receptors could markedly reduce the development of hypertrophy.(4) In normal rats, after treatment with FODA for 4 weeks, the heart weightindices were greatly increased as compared with control group (p<0.05)showing a formation of moderate hypertrophy albeit no changes in cardiacfunction were observable. (5) The cAMP production of hypertrophiedmyocardium (in group A) induced by FODA stimulation was greatly higher thanthat of control group (p<0.05) indicating that the responsiveness of dopamineD1-receptors was enhanced in hypertrophied myocardium. Conclusion (1) Stimulation or inhibition of cardiac dopamine D1-receptors could promote or inhibit respectively the development of myocardialhypertrophy, suggesting that cardiac dopamine D1-receptors are involved in theformation of myocardial hypertrophy under pathologic conditions. (2) Theresponsiveness of cardiac dopamine D1-receptors was greatly enhanced in thehypertrophied myocardium caused by pressure overload. (3) The cAMPsignalling pathway mediated by cardiac dopamine D1- receptors might beinvolved in the mechanism of myocardialhypertrophy.