Effects of metoclopramide and metoclopramide/dopamine on blood pressure and insulin release in normotensive, hypertensive, and type 2 diabetic subjects.
The objective is to determine cardiovascular and insulin release effects under metoclopramide (MTC) and dopamine (DA) infusion by using an acute comparative design with the intravenous infusion of both drugs. We evaluated 15 normal (normotensive and normoglycemic) subjects, 13 hypertensive, and 15 type 2 diabetic subjects. Subjects were submitted to an experimental design in which we first gave them a 0.9% saline solution for 30 minutes, and then administered MTC at 7.5 microg kg min through an intravenous infusion during a period of 30 minutes. Although subjects were receiving MTC, we added an intravenous infusion of DA at 1-3 microg kg min during 30 minutes. Blood pressure, heart rate, serum lipid profile, and insulin levels were measured. Sympathetic reactivity by the cold pressor test was also measured. In normotensive subjects, there was a systolic blood pressure and heart rate increase during MTC plus DA infusion. In subjects with diabetes mellitus there was a heart rate increase without changes in blood pressure during the MTC plus DA infusion period. In hypertensive subjects, MTC induced a significant decrease of systolic and diastolic blood pressure. During MTC plus DA period there was an increase of heart rate but no significant changes in blood pressure. During cold pressor test in both diabetic and hypertensive subjects, there were significant increases of both blood pressure and heart rate. Insulin serum levels increased in normotensive and hypertensive subjects but were attenuated in subjects with diabetes mellitus. We conclude that there is a pharmacologic interaction between MTC and DA, that the pressor effects of DA are due to activation to beta and alpha adrenergic receptors, and that the cardiovascular effects of DA in type 2 diabetic subjects are attenuated by a probable defect in sympathetic system and to endothelial dysfunction.
Contreras
Freddy
F
Clinical Pharmacology Unit, Vargas Medical School, Central University of Venezuela, Caracas, Venezuela. sicontreras@cantv.net
Fouillioux
Christian
C
Lares
Mary
M
Bolívar
Hector
H
Hernández
Rafael Hernández
RH
Velasco
Manuel
M
Cano
Raquel
R
Chacin
Maricarmen
M
Bermúdez
Valmore
V
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D003080:Cold Temperature; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D007328:Insulin; D008055:Lipids; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D008787:Metoclopramide; D004298:Dopamine