Decreased baroreflex sensitivity in isoproterenol-treated mice with cardiac hypertrophy.
The baroreflex has been shown to be impaired in rat models of cardiac hypertrophy. In the present study, we investigated the effects of beta-adrenoceptor-induced cardiac hypertrophy on the baroreflex in mice. Male Swiss Webster mice weighing 20-25 g were treated with the beta-adrenoceptor agonist isoproterenol (IPM; 15 microg/g/day, s.c.) for 7 days or with vehicle (control, CM). After treatment, IPM (n=9) and CM (n=9) were anesthetized with ketamine + xylazine (91.0: 9.1 mg/kg, i.p.) and had their carotid artery and jugular vein cannulated to test the arterial baroreflex. The baroreflex was evaluated by measuring changes in heart rate (HR) in response to acute increases and decreases in mean arterial pressure (MAP) induced by bolus injections of phenylephrine and sodium nitroprusside (1.5-24.0 microg/kg, i.v.) in conscious animals. IPM showed an increased cardiac weight/body weight (1.18 +/- 0.03 mg/g) ratio compared to CM (0.95 +/- 0.03 mg/g, p<0.05), but similar values of resting MAP (108 +/- 4 vs. 111 +/- 2 mm Hg) and HR (606 +/- 25 vs. 629 +/- 26 bpm). Sigmoidal barocurve analysis showed that isoproterenol treatment significantly reduced the following parameters: baroreflex sensitivity (IPM: -4.26 +/- 0.19 vs. CM: -5.92 +/- 0.54 bpm/mm Hg, p<0.05), reflex bradycardia plateau (IPM: 387 +/- 26 vs. CM: 318 +/- 19 bpm, p<0.05) and HR range (IPM: 369 +/- 30 vs. CM: 442 +/- 20 bpm, p<0.05). Linear regression analysis of baroreflex function also showed a diminished reflex bradycardia (CM: -8.92 +/- 0.87 bpm/mm Hg vs. IPM: -4.94 +/- 0.52 bpm/mm Hg, p<0.05), but similar reflex tachycardia (CM: -3.88 +/- 0.45 bpm/mm Hg vs. IPM: -3.52 +/- 0.43 bpm/mm Hg). In conclusion, beta-adrenoceptor-induced cardiac hypertrophy in mice led to impaired sensitivity of the cardiac baroreflex, which could be due to a diminished vagal activity to the heart.
Laboratory of Transgenes and Cardiovascular Control, Physiological Sciences Graduate Program, Biomedical Center, Federal University of Espirito Santo, Av Marechal Campos 1468, 29042-755 Vitoria, ES, Brazil.
Agata L
AL
Gava
Veronica A
VA
Peotta
Antonio M
AM
Cabral
Silvana S
SS
Meyrelles
Elisardo C
EC
Vasquez
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D001993:Bronchodilator Agents / Q000627:therapeutic use; D006332:Cardiomegaly / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006321:Heart; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009599:Nitroprusside / Q000494:pharmacology; D009929:Organ Size / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001993:Bronchodilator Agents; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D010656:Phenylephrine; D007545:Isoproterenol