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 endothelin (ET)-1 showed an elevation of arterial blood pressure (AP) and supplied an evidence for intrinsic ET-1 as one of the physiological regulators of systemic AP. Little is yet known, however, why deficiency of ET-1, which was originally found as a potent vasoconstrictor, led to higher AP in these mice. To address this apparent paradox, we first developed a method to measure renal sympathetic nerve activity (RSNA) in mice using rats as reference and successively compared it between normal 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 RSNA in ET-1 deficient mice (105+/-2 mmHg and 9.71+/-1.49 muVs, n=20) were significantly higher than those in wild-type mice (96+/-2 mmHg and 5. 07+/-0.70 muVs, n=25). Basal heart rate (HR) and baroreflex-control of HR was not significantly different between the two. On the other hand, resting RSNA, RSNA range, and maximum RSNA were significantly greater in ET-1 deficient mice, and thus MAP-RSNA relationship was upwards reset. Hypoxia-induced increase in RSNA was not different 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). These results indicate that endogenous ET-1 participates in the central chemoreception of CO2 and reflex control of the RSNA. Baroreceptor resetting and normally preserved hypoxia-induced chemoreflex may explain a part of the elevation of AP in ET-1 deficient mice.
Department of Physiology, School of Medicine, Chiba University, Chiba 260-8670, Japan.
G Y
GY
Ling
W H
WH
Cao
M
M
Onodera
K H
KH
Ju
H
H
Kurihara
Y
Y
Kurihara
Y
Y
Yazaki
M
M
Kumada
Y
Y
Fukuda
T
T
Kuwaki
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D002319:Cardiovascular System / Q000294:innervation; D002628:Chemoreceptor Cells / Q000502:physiology; D019332:Endothelin-1 / Q000235:genetics*; D006935:Hypercapnia / Q000503:physiopathology; D006977:Hypertension, Renal / Q000503:physiopathology; D007668:Kidney / Q000294:innervation*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000502:physiology; D012018:Reflex / Q000502:physiology; D012119:Respiration; D013564:Sympathetic Nervous System / Q000737:chemistry / Q000502:physiology*
D019332:Endothelin-1; D017466:Receptors, Endothelin