Role of the sympathetic nervous system in Schlager genetically hypertensive mice.
Early studies indicate that the hypertension observed in the Schlager inbred mouse strain may be attributed to a neurogenic mechanism. In this study, we examined the contribution of the sympathetic nervous system in maintaining hypertension in the BPH/2J mouse and used c-Fos immunohistochemistry to elucidate whether neuronal activation in specific brain regions was associated with waking blood pressure. Male hypertensive (BPH/2J; n=14), normotensive (BPN/3J; n=18), and C57/Bl6 (n=5) mice were implanted with telemetry devices, and after 10 days of recovery, recordings of blood pressure, heart rate, and locomotor activity were measured to determine circadian variation. Mean arterial pressure was higher in BPH/2J than in BPN/3J or C57/Bl6 mice (P<0.001), and BPH/2J animals showed exaggerated day-night differences (17+/-2 versus 6+/-1 mm Hg in BPN/3J or +8+/-2 mm Hg in C57/Bl6 mice; P<0.001). Acute sympathetic blockade with pentolinium (7.5 mg/kg IP) during the active and inactive phases reduced blood pressure to comparable levels in BPH/2J and BPN/3J mice. The number of c-Fos-labeled cells was greater in the amygdala (+180%; P<0.01), paraventricular nucleus (+110%; P<0.001), and dorsomedial hypothalamus (+48%; P<0.001) in the active (hypertensive) phase in BPH/2J compared with BPN/3J mice. The level of neuronal activation was mostly similar in these regions in the inactive phase. Of all of the regions studied, neuronal activation in the medial amygdala, as detected by c-Fos, was highly correlated to mean arterial pressure (r=0.98). These findings indicate that the hypertension is largely attributable to sympathetic nervous system activity, possibly generated through greater levels of arousal regulated by neurons located in the medial amygdala.
Davern
Pamela J
PJ
Neuropharmacology Laboratory, Baker IDI Heart and Diabetes Research Institute, 75 Commercial Road, Melbourne, St Kilda Road Central, Melbourne, Victoria 8008, Australia.
Nguyen-Huu
Thu-Phuc
TP
La Greca
Luisa
L
Abdelkader
Amany
A
Head
Geoffrey A
GA
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010425:Pentolinium Tartrate / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D000959:Antihypertensive Agents; D016760:Proto-Oncogene Proteins c-fos; D010425:Pentolinium Tartrate