Pathophysiology of obesity-related hypertension: role of insulin and the sympathetic nervous system.
Reviewed herein are data supporting the hypothesis that insulin and the sympathoadrenal system are involved in the pathogenesis of hypertension in the obese. Data from the Normative Aging Study, a population-based cohort followed in Boston, confirm other epidemiologic reports of a direct relationship between upper-body obesity, hyperinsulinemia, and hypertension. Because insulin is known to stimulate the sympathetic nervous system (SNS), the possibility that insulin-mediated sympathetic stimulation contributed to hypertension in the obese was investigated by the analysis of 24-h urinary norepinephrine (NE) excretion in this group. Urinary NE was directly correlated with body mass index and waist/hip ratio, supporting increased SNS activity in the obese. Epinephrine excretion, an index of adrenal medullary activity, was inversely related to obesity, and both high insulin and low epinephrine levels were independently correlated with lower levels of high-density lipoprotein cholesterol and higher levels of triglycerides. These results are consistent with the hypothesis that insulin-mediated sympathetic stimulation results in hypertension from concomitant sympathetic stimulation of the heart, vessels, and kidney. Reciprocal changes in adrenal medullary function contribute to the associated dyslipidemia. Therapeutic strategies aimed at diminishing insulin resistance and lowering insulin levels, and antagonizing the effects of sympathetic stimulation on the heart, the vessels, and the kidneys, would appear to have a solid physiological rationale in the obese.
Landsberg
L
L
Department of Medicine, Northwestern Medical School, Chicago, Illinois 60611.
D000818:Animals; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000628:therapy; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D012307:Risk Factors; D013564:Sympathetic Nervous System / Q000502:physiology*
D007328:Insulin; D008055:Lipids