Renal sympathetic nerve activity in mice: comparison between mice and rats and between normal and endothelin-1 deficient mice

• Published in: Brain research 1998-10, Vol.808 (2), p.238-249
• Main Authors: Ling, Guang-Yi, Cao, Wei-Hua, Onodera, Makoto, Ju, Ki-Hwan, Kurihara, Hiroki, Kurihara, Yukiko, Yazaki, Yoshio, Kumada, Mamoru, Fukuda, Yasuichiro, Kuwaki, Tomoyuki
• Format: Article
• Language: English
• Subjects: Animals; Baroreceptor reflex; Biological and medical sciences; Blood Gas Analysis; Blood pressure; Blood Pressure - physiology; Cardiovascular System - innervation; Chemoreceptor Cells - physiology; Chemoreceptor reflex; Endothelin receptors; Endothelin-1 - genetics; Fundamental and applied biological sciences. Psychology; Gene targeting; Hypercapnia - physiopathology; Hypertension; Hypertension, Renal - physiopathology; Kidney - innervation; Male; Medulla Oblongata - physiology; Mice; Mice, Knockout; Pressoreceptors - physiology; Rats; Rats, Sprague-Dawley; Receptors, Endothelin - physiology; Reflex - physiology; Respiration; Sympathetic Nervous System - chemistry; Sympathetic Nervous System - physiology; Vertebrates: urinary system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(98)00848-8

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 μVs, n=20) were significantly higher than those in wild-type mice (96±2 mmHg and 5.07±0.70 μVs, 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% CO 2). These results indicate that endogenous ET-1 participates in the central chemoreception of CO 2 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.