Published Online
on January 5, 2004

A more recent version of this article appeared on February 1, 2004

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Submitted on September 30, 2003
Revised on November 3, 2003

20-HETE and Circulating Insulin in Essential Hypertension With Obesity

Cheryl L. Laffer^*; Michal Laniado-Schwartzman; Alberto Nasjletti; and Fernando Elijovich

From Department of Medicine (C.L.L., F.E.), Lenox Hill Hospital, NYU School of Medicine, New York, and Department of Pharmacology (M.L.-S., A.N.), New York Medical College, Valhalla.

^* To whom correspondence should be addressed. E-mail: claffer{at}lenoxhill.net.

Abstract--Analogous to observations in Dahl salt-sensitive (SS) rats, we have shown that 20-hydroxyeicosatetraenoic acid (20-HETE) is involved in the pathogenesis of SS essential hypertension. A strong negative correlation between urine 20-HETE and body mass index (BMI) remains unexplained. We measured BP, urine sodium (UNaV), and 20-HETE in obese hypertensive subjects during a 24-hour salt load (160 mmol NaCl diet+2 L intravenous saline). We classified them into insulin-resistant (IR) (n=14) and insulin-sensitive (IS) (n=12), with the average insulin sensitivity index (SI=22.5x[fasting glucosexinsulin]^-1) of 3 days (cutoff for IR, SI <0.161 mL · L/µU · mmol). IR were older (50±1 versus 44±2, P<0.03), more obese (BMI 38.2±1.4 versus 32.0±1.5 kg/m², P<0.01), and had higher insulin (39.2±2.3 versus 22.0±1.1 µU/mL, P<0.0001) and lower SI (0.084±0.009 versus 0.222±0.013, P<0.0001) than IS. Blood pressure, UNaV, and sodium balance did not differ between groups. SI correlated negatively with age (r=-0.39, P<0.05) and BMI (r=-0.53, P<0.01). Urine 20-HETE was less in IR than in IS when normalized by serum insulin (0.91±0.25 versus 2.24±0.46 µg · 24 hours^-1/µU · mL^-1, P<0.02), but not if uncorrected. Urinary 20-HETE excretion correlated negatively with insulin (r=-0.40, P<0.04), whereas the relationship between 20-HETE and SI was not statistically significant. Our data suggest that increased circulating insulin, not the state of insulin resistance, suppresses urine 20-HETE excretion in obese hypertensive subjects. Findings in experimental models suggest that an inhibitory effect of insulin on cytochrome P4504A, rather than effects of insulin on membrane-bound arachidonic acid or on its release to the cytosol, may explain our observation.

Key words: hypertension • obesity • arachidonic acid • insulin • insulin resistance

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