Blunted central bromocriptine-induced tachycardia in conscious, malnourished rats.
Bromocriptine-induced tachycardia, persisting after adrenalectomy, is mediated by central dopamine D2 receptor stimulation through activation of the sympathetic outflow to the heart. The present study investigated the effects of malnutrition during pregnancy on bromocriptine-induced tachycardia in adult conscious rats. Malnourished rats were obtained by feeding dams a multideficient diet (providing 8% protein) during mating and pregnancy. Birth weight was significantly reduced in malnourished rats when compared to control rats born to dams fed standard commercially diet (23% protein) during mating and pregnancy. Baseline mean aortic pressure and heart rate in malnourished rats were comparable to those of well-nourished rats. Tachycardia (33+/-9 beats/min.), but not the hypotensive response to intravenous bromocriptine (150 microg/kg) was significantly reduced in malnourished rats, compared with control rats (70+/-10 beats/min.). In malnourished rats, pretreatment with intravenous domperidone (500 microg/kg) blocked the bromocriptine-induced hypotension, without affecting the tachycardia. Neither cardiac vagal (40+/-6 beats/min.) nor sympathetic tone (76+/-6 beats/min.) was significantly altered by multideficient diet-induced malnutrition (51+/-6 and 67+/-10 beats/min., respectively). In isolated perfused heart preparations from malnourished rats, positive inotropic response to isoproterenol (10-8 to 10-4 M) was not significantly different compared to that in control rats. In summary, malnutrition during foetal life blunted the bromocriptine-induced tachycardia, an effect that could be related to central dopamine D2 receptor desensitization rather than to impairment of autonomic regulation of the heart or cardiac beta-adrenoceptor desensitization.
Lahlou
Saad
S
Depart,ent of Physiology and Pharmacology, Center of Biological Sciences, Federal University of Pernambuco, 50670-901 Recife, PE, Brazil. lahlou@npd.ufpe.br
Araújo Lima
Paula F
PF
Interaminense
Leylliane F L
LF
Duarte
Gloria Pinto
GP
D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight / Q000187:drug effects; D001971:Bromocriptine / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D018491:Dopamine Agonists / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009748:Nutrition Disorders / Q000150:complications*; D011247:Pregnancy; D011248:Pregnancy Complications; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced* / Q000503:physiopathology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D002316:Cardiotonic Agents; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D007545:Isoproterenol