Heritability of free and receptor-bound leptin in normal twins.

Free and receptor-bound leptin may be regulated by different mechanisms. Genes that influence the concentration of these fractions may have an important functional bearing. We determined circulating leptin receptor concentrations, bound as well as free leptin concentrations, and body composition in 24 monozygotic (MZ) and in 22 dizygotic (DZ) twin pairs.

Influence of St John's wort on catecholamine turnover and cardiovascular regulation in humans.

Background: St John's wort (Hypericum perforatum) is a popular over-the-counter antidepressant. Its antidepressive effect has been attributed in part to inhibition of monoamine transporters and monoamine oxidase, on the basis of in vitro studies.

Methods: In a double-blind, randomized, placebo-controlled, crossover study, 16 healthy subjects (11 men and 5 women; mean age, 31 +/- 5 years) ingested either St John's wort (300 mg three times daily) or placebo for 7 days.

Adrenergic responsiveness of adipose tissue lipolysis in autonomic failure.

The sympathetic nervous system mobilizes lipids from adipose tissue through stimulation of beta-adrenergic receptors. The increase in lipid supply augments lipid oxidation. Patients with autonomic failure provide a unique opportunity to further elucidate the role of the adrenergic system in adipose tissue metabolism.

Phenotypical evidence for a gender difference in cardiac norepinephrine transporter function.

Norepinephrine transporter (NET) function has a central role in the regulation of synaptic norepinephrine concentrations. Clinical observations in orthostatic intolerance patients suggest a gender difference in NET function. We compared the cardiovascular response to selective NET inhibition with reboxetine between 12 healthy men and 12 age-matched women.

Water-induced thermogenesis.

Drinking lots of water is commonly espoused in weight loss regimens and is regarded as healthy; however, few systematic studies address this notion. In 14 healthy, normal-weight subjects (seven men and seven women), we assessed the effect of drinking 500 ml of water on energy expenditure and substrate oxidation rates by using whole-room indirect calorimetry. The effect of water drinking on adipose tissue metabolism was assessed with the microdialysis technique.

Heritability of venous function in humans.

Objective: Venous function contributes to the pathogenesis of thrombophlebitis, venous thrombosis, and possibly to arterial hypertension. Venous disease is presumably heritable; however, the genetic variance of venous function is unknown.

Methods And Results: We determined the heritability of venous function in 46 twin pairs (24 monozygotic, age 35+/-11 years, 14 men, 34 women; 22 dizygotic, age 30+/-8 years, 19 men, 25 women).

Water drinking acutely improves orthostatic tolerance in healthy subjects.

Background: Orthostatic symptoms and syncope are common, even in apparently healthy subjects. In patients with severe autonomic dysfunction, water drinking elicits an acute pressor response and improves orthostatic hypotension. We tested the hypothesis that water drinking also improves orthostatic tolerance in healthy subjects.

Paradoxical effect of sibutramine on autonomic cardiovascular regulation.

Background: Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment. Norepinephrine reuptake inhibition with sibutramine conceivably could exacerbate arterial hypertension and promote cardiovascular disease.

Methods And Results: In 11 healthy subjects (7 men, age 27+/-2 years, body mass index 23.

Acute effect of water on blood pressure. What do we know?

Water drinking elicits a large, acute, pressor response in patients with autonomic failure who experience severe orthostatic hypotension. This essentially cost-free intervention has been successfully employed therapeutically in these patients to attenuate orthostatic and postprandial hypotension. In orthostatic intolerance patients, water drinking blunts the orthostatic tachycardia but has only a modest effect on blood pressure.

Catechol-o-methyltransferase and blood pressure in humans.

Background: Whether catechol-O-methyltransferase (COMT), the enzyme that metabolizes extraneuronal norepinephrine, contributes to blood pressure regulation in humans is unknown.

Methods And Results: We studied incremental doses of the COMT inhibitor entacapone, the sympathetic stimulant yohimbine, and placebo in 7 patients with multiple system atrophy (Shy Drager syndrome). We selected these unique subjects because norepinephrine exerts an exaggerated increase in blood pressure in these patients.

Baroreflex buffering and susceptibility to vasoactive drugs.

Background: The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known.

Methods And Results: We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects.