Blood pressure of endothelin-3 null (-/-) knockout mice and endothelin A receptor null (-/-) knockout mice under anaesthesia

Blood pressure (BP) and heart rate (HR) in endothelin-3 (ET-3) null (-/-) knockout mice and ET_A receptor (-/-) mice were measured using the servo null pressure measuring technique under halothane anaesthesia. In infant ET-3 (-/-) mice (2–3 weeks old), mean BP and HR were 55±2mmHg and 436±30beats/min respectively. These values were not different from those in age-matched wild-type mice (53±3mmHg and 430±18beats/min respectively). Baroreflex sensitivity, which was calculated as the slope of the relationship between systolic BP and RR interval on an ECG, was also similar in ET-3 (-/-) mice (0.84±0.20ms/mmHg) and wild-type mice (1.07±0.38ms/mmHg). ET_A receptor (-/-) mice were obtained by caesarean section on the expected day of delivery and tracheotomized, so that they would live for more than 24h. Mean BP and HR in ET_A receptor (-/-) mice were 15±1mmHg and 333±6beats/min respectively. These values were not different from those in age-matched, similarly treated wild-type mice (16±3mmHg and 308±10beats/min respectively). Baroreflex sensitivity in the newborn ET_A receptor (-/-) mice (0.45±0.15ms/mmHg) and wild-type mice (0.31±0.06ms/mmHg) were very low compared with the values in infant wild-type mice, but not different between the mutant mice and their littermates. Moreover, HR in awake ET_A receptor (-/-) mice (396±13beats/min) was not different from that in wild-type mice (409±13beats/min). These results show that the ET_A receptor and ET-3 are not involved in cardiovascular regulation, at least during the very early life of the mice. A possible involvement of the ET_A receptor in BP regulation, if any, seems to occur at later times and/or in some pathological settings.