endothelin-1 and Hypotension--Orthostatic

Syncope is a symptom, defined as a transient, self-limited loss of consciousness, usually leading to falling. Syncope is a common clinical problem accounting for 5% of hospital admissions and up to 3-5% of emergency department visits. Neurocardiogenic syncope is the most frequent. Vasovagal syncope, carotid sinus syndrome and glossopharyngeal and trigeminal neuralgia are numbered. Clinical descriptions of familial vasovagal syncope are scarce. Studies indicate a strong heritable component to the etiology of vasovagal syncope in over 20% of cases. There are no published molecular genetic studies in vasovagal syncope. There are several studies evaluating gene polymorphism in orthostatic hypotension and intolerance: the endothelin-1 gene (insertion variant in the 5'UTR), B1-adrenergic receptor gene (polymorphism beta1Gly49), the human norepinephrine transporter gene (polymorphism Ala457Pro), Gs protein alpha-subunit (polymorphism T131C) and G-protein beta 3 subunit (polymorphism C825T), and SCNN1G gene encoding the gamma subunit of the amilorid-sensitive epithelial sodium channel. Moreover there are reported the presence of multiple point mutations in the mitochondrial DNA (mtDNA) in three families with orthostatic hypotension. Molecular genetic studies in vasovagal syncope make possible the further explanation of the pathophysiology and the evaluation of individual prognosis and optimal management.

Topics: Adolescent; Adult; Aged; Autonomic Nervous System; Autonomic Nervous System Diseases; Child; Child, Preschool; Endothelin-1; Genetic Variation; Humans; Hypotension, Orthostatic; Middle Aged; Pedigree; Prognosis; Syncope, Vasovagal

Orthostatic intolerance is a multifactorial disease in which the genetic contribution is probably the result of a number of genes acting in combination. Recent work has shown that orthostatic intolerance is influenced by endothelial nitric oxide synthase gene polymorphisms. Since endothelin-1 (ET-1) is one of the most important vasoconstrictor peptides, a frequent adenine insertion polymorphism within the 5'-untranslated region (5'UTR), which is of functional importance for ET-1 expression, could influence orthostatic intolerance. The aim of this study was therefore to ascertain whether this frequent variant of the endothelin-1 gene influences the risk for orthostatic intolerance.. We studied 257 white patients (120 cases with orthostatic intolerance and 137 controls) for genotyping of the 5'UTR I variant. From this cohort, 111 patients and 99 control subjects underwent a tilt-table test or an upright posture study, including monitoring of blood pressure, heart rate, and plasma catecholamines, in the supine position and during 30 minutes of standing. Genotyping was performed in all participants. Chi tests of independence were used to test for associations between orthostatic intolerance and genotype. In addition, an association of the insertion polymorphism with hemodynamic variables (heart rate, supine and upright blood pressure) was ascertained using one-way analysis of variance.. The 5'UTR I variant was significantly less common in patients with orthostatic intolerance (allele frequency 0.36 and 0.28, in controls and cases, respectively). Additionally, we found a significant decrease in the risk of orthostatic intolerance among people who were homozygous for the 5'UTR variant (I/I) compared with the wild-type variant (D/D) (odds ratio, 0.41; 95% confidence interval, 0.17 to 0.97; P = 0.04). No association between the 5'UTR variant and heart rate or blood pressure regardless of diagnosis was found.. Our current results suggest that the hereditary adenine insertion variant in the 5'-UTR of the endothelin-1 gene is protective for orthostatic intolerance. The increased ET-1 protein expression that has been linked with the I variant might be associated with a more efficient hemodynamic response to standing. This is likely one of several common genetic loci that may represent modifiers of orthostatic intolerance phenotypes.

Topics: 5' Untranslated Regions; Adult; Alleles; Endothelin-1; Female; Genetic Variation; Genotype; Humans; Hypotension, Orthostatic; Male

A possible relationship between endurance exercise training, susceptibility to motion sickness, and orthostatic tolerance was investigated. Male subjects underwent acceleration tolerance tests, lower body negative pressure, and Coriolis tests. During the experimental protocol, hemodynamic parameters were measured including heart rate, stroke volume, blood pressure, and cardiac output, and blood was drawn and analyzed for various hormones. Specific results are presented and discussed.

Topics: Acceleration; Adult; Aerospace Medicine; Atrial Natriuretic Factor; Disease Susceptibility; Endothelin-1; Hemodynamics; Humans; Hypotension, Orthostatic; Lower Body Negative Pressure; Male; Motion Sickness; Physical Endurance; Physical Fitness; Renin; Rotation