Effect of dopamine on vascular reactivity in near-term lamb carotids: role of the endothelium.
Many neonates are diagnosed with hypotension in the first 24 hr of life. Those with severe hypotension are often given high doses of dopamine at 10 to 20 microg/kg/min. This study examined the hypothesis that dopamine, a vasoactive drug commonly used in the neonatal intensive care unit, alters vascular reactivity. Vascular reactivity was measured by comparing 5HT dose-response characteristics in untreated near-term lamb common carotid arteries and arteries treated with 15 microg/kg/min of dopamine. The authors found that dopamine pretreatment for 60 min significantly potentiated 5HT-induced contractile tone by approximately 100% ( p < .05). This observed increase in tone was accompanied by a significant decrease in the affinity of 5HT to its receptor ( p < .05), suggesting an activation of a separate contractile pathway, or a mechanism downstream from agonist-receptor binding. Interestingly, an increase in contractility was observed only in endothelium-intact arteries. In arteries with denuded endothelium, dopamine pretreatment resulted in a small but significant decrease in tone compared to control arteries ( p < .05), suggesting a vasodilatory mechanism unmasked by endothelium removal. Although multiple mechanisms can increase vascular resistance, these data described the in vitro effects of high doses of dopamine on vascular tone as well as the role of the endothelium in dopaminemediated vasoconstriction.
Angeles
Danilyn M
DM
Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. dangeles@som.llu.edu
Pearce
William J
WJ
D000818:Animals; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007022:Hypotension / Q000188:drug therapy / Q000503:physiopathology; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D012756:Sheep; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D015259:Dopamine Agents; D014665:Vasodilator Agents; D010643:Phenoxybenzamine; D012701:Serotonin; D004298:Dopamine