Reduction in resting metabolic rate and ratio of plasma leptin to urinary nitric oxide: influence on obesity-related hypertension.
BACKGROUND
Multiple factors are involved in the pathogenesis of hypertension in the obese individual


OBJECTIVE
To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.


METHODS
We evaluated three groups: 25 obese hypertensive patients (age 45.7 +/- 1.37 years, body mass index 34.2 +/- 1.35 kg/m2, systolic/diastolic blood pressure 155 +/- 2.9/105 +/- 1.3, mean arterial pressure 122 +/- 1.50 mmHg); 21 obese normotensive patients (age 39.6 +/- 1.72, BMI 31.3 +/- 0.76, SBP/DBP 124 +/- 2.1/85.4 +/- 1.8, MAP 98.2 +/- 1.80); and 17 lean normotensive subjects (age 38.1 +/- 2.16, BMI 22.1 +/- 0.28, SBP/DBP 117 +/- 1.7/76.8 +/- 1.5, MAP 90.1 +/- 1.50). We determined basal resting metabolic rates, plasma insulin (radio-immunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n = 14) and 14 (n = 10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.


RESULTS
Obese hypertensive patients had significantly higher basal RMR and plasma NE levels insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than in obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP, RMR, and plasma NE and insulin. Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.


CONCLUSIONS
A reduction in sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.
Golan
Eliezer
E
Department of Nephrology and Hypertension, Meir Hospital, Kfar Saba, Israel. golanel@clalit.org.il
Tal
Bruria
B
Dror
Yossef
Y
Korzets
Ze'ev
Z
Vered
Yaffa
Y
Weiss
Eliyahu
E
Bernheim
Jacques
J
D000328:Adult; D000704:Analysis of Variance; D001481:Basal Metabolism / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D004038:Diet, Reducing; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000652:urine*; D009638:Norepinephrine / Q000097:blood; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D011863:Radioimmunoassay
D007328:Insulin; D020738:Leptin; D009569:Nitric Oxide; D009638:Norepinephrine