Vascular insulin abnormalities, hypertension, and accelerated atherosclerosis.
There is accumulating evidence that insulin resistance, glucose intolerance, and hyperinsulinemia exist in people with high blood pressure, and it has been suggested that insulin resistance and hyperinsulinemia may be of great importance in the origin of hypertension and its ultimate clinical course. Of importance are the recent observations that persons with normal glucose tolerance, selected on the basis of hyperinsulinemia, had higher blood pressure than matched individuals with normoinsulinemia. Hypertension in in insulin-resistant states generally has been attributed to hyperinsulinemia, with resulting increases in sympathetic nervous system activity. However, recent data from our laboratory suggest that cellular insulin resistance rather than hyperinsulinemia per se may lead to hypertension. The basic tenet proposed in this article is that a deficiency of insulin at the cellular level represents a common mechanism that is involved in the development of hypertension in both type I and type II diabetes mellitus. Insulin has an important role in the modulation of cellular calcium metabolism. Decreased insulin action on vascular smooth muscle cells may contribute both to hypertension and to accelerated atherosclerosis. Recent observations suggest that an impaired cellular response to insulin predisposes to increased vascular smooth muscle tone (the hallmark of hypertension in the diabetic state). For example, recently reported studies from our laboratory demonstrate that insulin attenuates the vascular contractile response to phenylephrine, serotonin, and potassium chloride. Thus, it appears that insulin normally modulates (attenuates) vascular smooth muscle contractile responses to vasoactive factors, and insulin resistance should accordingly be associated with enhanced vascular reactivity.
Division of Endocrinology, Hypertension and Vascular Medicine, Wayne State University School of Medicine, Detroit, MI.
P R
PR
Standley
M H
MH
Bakir
J R
JR
Sowers
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications* / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*