title: Prenatal cocaine alone and combined with nicotine alters ANG II and IGF-1 induced left atrial contractions in aging male offspring.
abstract: Prenatal cocaine or nicotine affects inotropic activity in the hearts of rat offspring. However, the long-term consequence of this exposure on the cardiac response to hormonal challenge is unknown. We assessed the inotropic effects of angiotensin II (ANG II) and insulin-like growth factor 1 (IGF-1) in the left atria of 19.0-24.5 month-old male rats exposed on gestation days 8-21 to 1 of 6 treatments: low cocaine (LC) (20 mg/kg) or high cocaine (HC) (40 mg/kg); 20 mg/kg cocaine and high nicotine (5 mg/kg nicotine) (LC/HN); 40 mg/kg cocaine and low nicotine (2.5 mg/kg nicotine) (HC/LN); pair fed: yoked to HC (PF); saline: injection of 0.9% NaCl (SAL). Isometric contractions were assessed by electrical stimulation of isolated left atria superfused with Tyrode solution (control) to which ANG II (10-7 mol/L, 20 min) and IGF-1 (10-8 mol/L, 20 min) in the presence of ANG II were added sequentially. Offspring in all cocaine groups showed a higher peak tension development (PTD) to ANG II than PF controls. This increase in PTD was attenuated by subsequent addition of IGF-1 in all except HC offspring. However, with the HC/LN combination the IGF-1 effect on PTD was again evident. The velocities of contraction and relaxation were positively affected by ANG II only in the combined prenatal drug groups; IGF-1 reduced only contraction velocity. Our data demonstrate that IGF-1 reverses the positive inotropic effect of ANG-II in atrial muscle of aging rats and that gestational exposure to only high doses of cocaine eliminates this protective response. It appears that combined prenatal exposure to cocaine and nicotine does not exacerbate the decline in cardiac function and responsiveness to inotropic drugs seen in the aging heart.
authors.affiliation: Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC 20059, USA. ghaddad@howard.edu
authors.forename: Georges E
authors.initials: GE
authors.lastname: Haddad
authors.forename: Alexandre
authors.initials: A
authors.lastname: Scheer
authors.forename: Elijah
authors.initials: E
authors.lastname: Clarke
authors.forename: Jason K
authors.initials: JK
authors.lastname: Arguinzoni
authors.forename: Sonya K
authors.initials: SK
authors.lastname: Sobrian
mesh_terms: D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D009538:Nicotine; D003042:Cocaine