Evidence against a role for dopamine D1 receptors in the myocardium of the pig.
1. We investigated the presence of dopamine D1 receptors in the myocardium of anesthetized pigs using intravenous infusions of dopamine, alone and after alpha- and beta-adrenoceptor blockade and intracoronary infusions of the selective D1 receptor agonist, fenoldopam. 2. Intravenous infusion of dopamine (2.5, 5 and 10 micrograms kg-1 min-1 for 10 min, n = 6) caused dose-dependent changes in heart rate (from 94 +/- 6 to 132 +/- 10 beats min-1, P less than 0.05), the maximal rate of rise of left ventricular pressure (LVdP/dtmax; from 2280 +/- 170 to 4800 +/- 410 mmHgs-1, P less than 0.05), mean arterial blood pressure (from 87 +/- 5 to 62 +/- 3 mmHg) and systemic vascular resistance (from 40 +/- 4 to 28 +/- 2 mmHgl-1 min, P less than 0.05). The increases in heart rate and LVdP/dtmax were abolished when dopamine was infused after alpha- and beta-adrenoceptor blockade. The vasodilator response was, however, only minimally affected. 3. Intravenous infusions of dopamine decreased coronary vascular resistance from 0.90 +/- 0.06 to 0.53 +/- 0.07 mmHg ml-1 min 100 g (P less than 0.05). This action of dopamine was not observed when dopamine was infused after blockade of the alpha- and beta-adrenoceptors. 4. Pretreatment with alpha- and beta-adrenoceptor blockade had no effect or only slightly attenuated the dopamine-induced decrease in vascular resistance of the brain, kidneys, adrenals and small intestine. 5. In 7 animals, intracoronary doses of 0.04, 0.1, 0.2 and 0.4g kg1- min 1 of fenoldopam had no effect on coronary venous oxygen content, local myocardial oxygen consumption, coronary blood flow or coronary vascular resistance. However, systemic effects were observed at the highest two doses, as manifested by a drop in mean arterial blood pressure from 82 +/- 4 to 72 +/- 4mmHg (P < 0.05) due to peripheral vasodilatation (e.g. cerebral vascular bed). Heart rate, LVdP/dt,.,, regional myocardial segment length shortening and left ventricular end-diastolic pressure were not affected at these doses. In 2 animals the infusion rate was increased to 4jug kg1 min 1, but again there was no evidence for coronary vasodilatation. 6. We conclude that the intravenous infusion of dopamine after alpha- and beta-adrenoceptor blockade and the intracoronary infusion of fenoldopam provided no evidence for a major role of D1 receptors in the coronary circulation of pigs. The absence of any effect of the employed doses of fenoldopam on LVdP/dt.mx and on regional myocardial segment length shortening also indicates that fenoldopam does not exhibit any inotropic action in this species.
Laboratory for Experimental Cardiology, Thoraxcentre, Erasmus University Rotterdam, The Netherlands.
L J
LJ
Van Woerkens
D J
DJ
Duncker
M O
MO
Den Boer
E O
EO
McFalls
L M
LM
Sassen
P R
PR
Saxena
P D
PD
Verdouw
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D018818:Fenoldopam; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam; D004298:Dopamine