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.