Sympathetic nervous system in salt-sensitive and obese hypertension: amelioration of multiple abnormalities by a central sympatholytic agent.

Ernsberger P, Koletsky RJ, Collins LA, Bedol D

Department of Medicine, Case Western Reserve School of Medicine and St. Luke's
Medical Center, Cleveland, Ohio, USA.

Excess activity of the sympathetic nervous system (SNS) is linked to human
obese hypertension and to salt-sensitive hypertension. Paradoxically, reduced
SNS activity has been implicated as a contributor to obesity, particularly in
animal models, and salt loading usually inhibits SNS activity. We have
investigated the relationship between SNS activity, diet, and hypertension in
the obese spontaneously hypertensive rat (SHROB), a model with a recessive
obesity trait superimposed on a hypertensive background with multiple metabolic
abnormalities resembling human syndrome X. We examined the role of SNS
overactivity in the adverse impact of excess dietary salt and the possible
beneficial effects of sympatholytic therapy. Mean blood pressure (MBP) was
increased in SHROB and SHR fed a 4% NaCl diet. The pressor effect of dietary
salt was abolished by ganglionic blockade, suggesting that increased SNS
activity contributed to the pressor effect of the high-salt diet. Moxonidine, a
second-generation central antihypertensive, controlled hypertension in both
SHROB and SHR. Kidney damage in SHROB was accelerated by dietary salt and was
reduced by moxonidine. Moxonidine elicited progressive weight loss in SHROB but
not in SHR. Food intake in SHROB was reduced to the level of lean SHR. SHROB
and SHR treated with moxonidine showed improved glucose tolerance.
Additionally, SHROB showed reduced levels of triglycerides, cholesterol, and
insulin following moxonidine therapy. Inhibition of the SNS, as with moxonidine
therapy, may ameliorate multiple abnormalities and have therapeutic advantages
in obese hypertensive syndromes.