Dopamine in the conscious dog with chronic heart-block. Mechanisms of chronotropic cardiac effects.
The chronotropic effects of dopamine were studied in the conscious dog with chronic A-V block. Dopamine at 12.5-200 micrograms/kg and 12.5-50 micrograms/kg/min lowered atrial rate independently of dose. After blockade of muscarine receptors or alpha-adrenoceptors, it raised atrial rate. After blockade of dopamine receptors, dopamine still lowered atrial rate, and did so dose-relatedly after blockade of beta-adrenoceptors. It raised ventricular rate, and at high doses also induced ventricular rhythm disorders. Blockade of muscarine receptors enhanced the ventricular cardioaccelerator effect of dopamine (P less than 0.025) at 100 micrograms/kg, while blockade of alpha-adrenoceptors reduced it (P less than 0.05). Blockade of dopamine receptors did not modify this effect, but blockade of beta-adrenoceptors reversed it. Dopamine at 25-200 micrograms/kg raised mean blood pressure. This effect was enhanced by blockade of muscarine receptors, reversed by blockade of alpha-adrenoceptors, and was unaffected by blockade of beta-adrenoceptors or dopamine receptors. These results show that the atrial cardiomoderator effect of dopamine is a vagal reflex response to its hypertensive action, and that it is limited by its direct beta-adrenergic stimulating action. They also show that the ventricular cardioaccelerator effect of dopamine is attenuated by a reflex vagal depressor effect consequent to the induced hypertension. No evidence was found for the existence of positive chronotropic dopamine receptors in either atria or ventricles.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001283:Atrioventricular Node / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006327:Heart Block / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011954:Receptors, Dopamine / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D006220:Haloperidol; D004298:Dopamine