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(Hypertension. 1997;29:280.)
© 1997 American Heart Association, Inc.

Arthur C. Corcoran Memorial Lecture

Relationship Between Insulin Resistance and Endothelium-Dependent Vascular Relaxation in Patients With Essential Hypertension

Yukihito Higashi; Tetsuya Oshima; Nobuo Sasaki; Norio Ishioka; Yukiko Nakano; Ryoji Ozono; Mitsuisa Yoshimura; Katsuhiko Ishibashi; Hideo Matsuura; Goro Kajiyama

From the First Department of Internal Medicine (Y.H., N.S., N.I., M.Y., K.I., H.M., G.K.) and the Department of Clinical Laboratory Medicine (T.O., Y.N., R.O.), Hiroshima University School of Medicine, Japan.

Correspondence to Yukihito Higashi, MD, First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan

The infusion of L-arginine induces the production of nitric oxide and stimulates the immediate secretion of insulin. To examine the relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension, we evaluated the renal and insulin responses to L-arginine, 500 mg/kg infused intravenously over 30 minutes, in 23 patients with mild essential hypertension who were neither obese nor diabetic and in 20 normotensive control subjects. We found no difference between the two groups in blood glucose or insulin in the fasting condition. The renovascular relaxation induced by L-arginine was significantly less in patients with essential hypertension than in normotensive control subjects. The increase in plasma cyclic GMP in response to L-arginine was lower in hypertensive patients than in normotensive subjects. Although the serum concentrations of glucose in response to L-arginine were similar in the two groups, the serum insulin response of the essential hypertensives was significantly higher than that of the normotensive subjects. In all subjects, the peak cyclic GMP response to L-arginine was significantly correlated with the peak glucose/ insulin ratio response to L-arginine (r=.69, P<.001). Findings suggested that an impairment of endothelium-dependent renal vascular relaxation and a reduced sensitivity to insulin are present in patients with essential hypertension. A link may be present between the abnormality of the L-arginine/nitric oxide/cyclic GMP pathway and insulin resistance in patients with essential hypertension.

Key Words: L-arginine • nitric oxide • cyclic GMP • hypertension, essential • insulin resistance • renal circulation

Abbreviations: FF = filtration fraction • GFR = glomerular filtration rate • LDL = low-density lipoprotein • NO = nitric oxide • PAH = para-amino hippurate • PRA = plasma renin activity • RPF = renal plasma flow • RVR = renal vascular resistance

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