Correlation between apolipoprotein B and endothelin-1-induced vasoconstriction in humans.

Low-density lipoprotein (LDL) concentrations have been linked to altered responses to endogenous vasodilators and vasoconstrictors. We evaluated retrospectively the relationship between LDL and vasoconstrictor (endothelin-1, phenylephrine) responsiveness of the forearm vasculature in 15 elderly healthy volunteers with apolipoprotein B and LDL levels in the normal range. In contrast to phenylephrine, changes in forearm vascular resistance induced by endothelin-1 were correlated with apolipoprotein B, LDL, and total cholesterol concentrations in women but not in men. These findings might suggest that lipids may increase vascular tone through both impaired endothelial vasodilation and increased vasoconstriction to endothelin-1 at least in women.

[SIADH with epileptic seizures and coma in fluoxetine therapy]. / SIADH mit epileptischen Anfällen und Koma unter Fluoxetin-Therapie.

Hyponatremia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been associated with several psychotropic drugs e.g., carbamazepine, neuroleptics, tricyclic antidepressants and more recently selective serotonin reuptake inhibiting (SSRI) antidepressants. SSRIs have gained widespread use in elderly depressed patients because of their favourable adverse effect profile. However, SSRIs have recently been associated increasingly with SIADH. We describe a 82-year old patient who was hospitalised after witnessed convulsions ten days after initiation of fluoxetine therapy for depression. She had hyponatremia and increased urine osmolarity suggesting SIADH. Using this case we discuss the clinical symptoms, aetiology, differential diagnosis and therapy of drug-induced SIADH.

Neurokinin-1 receptor antagonist R116301 inhibits substance P-induced venodilation.

OBJECTIVE: To test the effect of the neurokinin-1 receptor antagonist hydroxybutanedioate (R116301) in human hand veins in vivo. METHODS: In a randomized, double-blind, placebo-controlled crossover study we used the hand vein compliance method to evaluate the inhibition of the response to substance P by R116301. RESULTS: In hand veins preconstricted with phenylephrine to 21% +/- 2.6% (mean +/- SEM, placebo) and 25% +/- 3.0% (R116301) of the initial diameter, substance P resulted in a mean venodilation of 84% +/- 7% and 87% +/- 13% (P = .8) before administration of placebo and R116301, respectively. Oral administration of 300 mg R116301 resulted in peak plasma concentrations of 1.16 +/- 0.1 microg/mL within 128 +/- 14 minutes. With increasing R116301 plasma concentrations, substance P-induced venodilation decreased significantly (P < .001), whereas placebo had no effect. Mean substance P-induced venodilation was markedly reduced to 8% +/- 7%. CONCLUSION: This study confirms the presence of neurokinin-1 receptors in human veins and the effectiveness of the neurokinin-1 receptor antagonist R116301 in human hand veins.

Inverse correlation between endothelin-1-induced peripheral microvascular vasoconstriction and blood pressure in glaucoma patients.

BACKGROUND: The potent vasoconstrictor peptide endothelin-1 has been shown to participate in the control of peripheral vascular tone and in the regulation of ocular perfusion. In glaucoma patients vasospasms and arterial hypotension have been identified as risk factors for the progression of glaucomatous damage, and the regulation of endothelin-1 release is disturbed in some of these patients. The aim of this study was to assess the relationship between resting blood pressure and cutaneous vascular responsiveness to endothelin-1 and phenylephrine in patients with glaucoma and in matched controls. METHODS: In 9 patients with primary open-angle glaucoma (POAG), 7 patients with normal tension glaucoma (NTG), and 16 age- and sex-matched controls, endothelin-1 and phenylephrine responses were assessed in the human forearm microcirculation using laser Doppler flowmetry during intra-arterial drug administration. Blood pressure was measured intra-arterially. RESULTS: In contrast to alpha 1-adrenergic effects, endothelin-1 responses were inversely correlated to both systolic (r2 = 0.27, P = 0.05) and diastolic (r2 = 0.54, P = 0.001) blood pressure in glaucoma patients, whereas there was no such correlation in controls. Patients with lower blood pressure values were more sensitive to the vasoconstrictor effects of endothelin-1. Cutaneous responsiveness to endothelin-1 and phenylephrine was similar in glaucoma patients and in controls. CONCLUSION: These results reveal that glaucoma patients appear to have peripheral microvascular abnormalities which are exhibited as altered responsiveness to endothelin-1. Thus, this study supports the hypothesis that endothelin-1-related microvascular dysfunction may be involved in the pathogenesis of glaucomatous damage.