BACKGROUND:
The baroreceptor reflex dampens short term fluctuations in blood pressure (BP) by feedback modulation of heart rate and sympathetic vasomotor activity. Impairment of this reflex occurs in hypertension and heart failure, possibly via an action of angiotensin II (AngII). AngII acts via its type 1A receptor (AT1AR) in the nucleus of the solitary tract to attenuate the baroreceptor reflex. Previously published work (Gembardt et al., FASEB J. 2008) reported thatAT1AR knockout mice show gross impairment in the baroreceptor reflex.
METHODS:
To understand the mechanism behind this impairment, arterial and cardiopulmonary baroreceptor reflexes were studied in isoflurane-anesthetized wild-type (WT) and AT1AR knockout mice at 3 and 7 months. BP was measured via an indwelling catheter in the common carotid artery and heart rate derived from this signal. Reflexes were activated by bolus injections or slow ramp infusions of phenylephrine and sodium nitroprusside through a catheter in the jugular vein.
RESULTS:
In the WT mice, reflex changes in heart rate were observed in response to induced alteration in BP as have been described by others. Responses were comparable between both protocols and between ages. In contrast to published data, no significant difference in either reflex response was observed between AT1AR knockout and WT mice at either age.
DISCUSSION
Our observations are in distinct contrast to the previous report and indicate no alteration in baroreceptor reflex function in AT1AR knockout mice. The principal difference between the studies lies in the anaesthetic used - isoflurane in this study and pentobarbital in the published report. The results presented in this study are consistent with observations made in conscious mice and suggest the observed differences may be due to responsiveness to pentobarbital anaesthesia.
CONCLUSIONS
There are no obvious alterations in the arterial and cardiopulmonary baroreceptor reflex function of AT1A KO mice at 3 and 7 months of age.