Sympathetic nervous system in salt-sensitive and obese hypertension: amelioration of multiple abnormalities by a central sympatholytic agent.
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.
Ernsberger
P
P
Department of Medicine, Case Western Reserve School of Medicine and St. Luke's Medical Center, Cleveland, Ohio, USA.
Koletsky
R J
RJ
Collins
L A
LA
Bedol
D
D
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000150:complications* / Q000503:physiopathology*; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011918:Rats, Inbred SHR; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013565:Sympatholytics / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D008055:Lipids; D013565:Sympatholytics; D012965:Sodium Chloride; C043482:moxonidine