RENAL SYMPATHETIC-NERVE ACTIVITY IN MICE - COMPARISON BETWEEN MICE AND RATS AND BETWEEN NORMAL AND ENDOTHELIN-1 DEFICIENT MICE

Recently generated knockout mice with disrupted genes encoding endothe lin (ET)-1 showed an elevation of arterial blood pressure (AP and supp lied an evidence for intrinsic ET-1 as one of the physiological regula tors of systemic AP. Little is yet known, however, why deficiency of E T-1, which was originally found as a potent vasoconstrictor, led to hi gher AP in these mice. To address this apparent paradox, we first deve loped a method to measure renal sympathetic nerve activity (RSNA) in m ice using rats as reference and successively compared it between norma l and ET-1 deficient mice. RSNA was successfully recorded in urethane- anesthetized and artificially ventilated mice by a slight modification of the method used for rats. At basal condition, mean AP (MAP) and RS NA in ET-1 deficient mice (105 +/- 2 mmHg and 9.71 +/- 1.49 mu Vs, n = 20) were significantly higher than those in wild-type mice (96 +/- 2 mmHg and 5.07 +/- 0.70 mu Vs, n = 25). Basal heart rate (HR) and baror eflex-control of HR was not significantly different between the two. O n the other hand, resting RSNA, RSNA range, and maximum RSNA were sign ificantly greater in ET-1 deficient mice, and thus MAP-RSNA relationsh ip was upwards reset. Hypoxia-induced increase in RSNA was not differe nt between ET-1 deficient (73.4 +/- 9.4%) and wild-type mice (91.2 +/- 12.0%), while hypercapnia-induced one was significantly attenuated in ET-1 deficient mice (18.8 +/- 3.6 vs. 39.1 +/- 5.2% at 10% CO2). Thes e results indicate that endogenous ET-1 participates in the central ch emoreception of CO2 and reflex control of the RSNA. Baroreceptor reset ting and normally preserved hypoxia-induced chemoreflex may explain a part of the elevation of AP in ET-1 deficient mice. (C) 1998 Elsevier Science B.V. All rights reserved.