Анатомия и физиология: текущие исследования
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ISSN: 2161-0940
ISSN: 2161-0940
Sebastian Mathes, Sander van Ginke, David Vaughan, Paola Valdivieso and Martin Flück
Angiotensin 2 is a major vasoconstrictor and subject to complex regulation. It is produced by the angiotensinconverting enzyme (ACE), which is itself regulated by blood flow and represents a target for pharmacological (lisinopril) and genetical (ACE-I/D polymorphism) influences. 32 healthy Caucasian men of British descent, including six subjects that were treated with lisinopril, completed standardized one-legged cycling-type endurance exercise to assess ACE-I/D and lisinopril dependent levels alterations of ACE and hypoxia-modulated transcripts in knee extensor muscle. Lisinopril treatment revealed significantly decreased transcript expression at baseline (COX4I1-88%; COX4I2 -67%; HIF-1α -93%) and 3 hours into recovery (HIF-1α -78%; ACE -62%). Furthermore, during recovery from cycling-type endurance exercise, COX4I2 mRNA expression was increased by 281% in ACE-II genotypes (p <0.05) but not in subjects carrying the ACE D-allele. Additionally, ACE-DD genotypes showed a trend for superior expression of ACE mRNA (p =0.07), whereas for carriers of the ACE I-allele a decrease (ACE-ID-35%; ACE-II -67%) was observed. Changes in COX4I2 and ACE transcript expression were correlated to HIF-1α protein levels prior to exercise, which was highest in ACE-DD genotypes. The interpretative hypothesis is suggested that exercise-induced COX4I2 transcript expression is sensitized in dependence of the I-allele, which silences ACE expression. The findings implicate a pronounced influence of anti-hypertensive treatment on muscle gene expression, which is modified by the ACE-I/D genotype. The observed effects of lisinopril and the ACE I-allele suggests a possible role of shear stress and tissue oxygenation on the expression of oxygen-associated transcripts during recovery from the sympatholytic challenge of endurance exercise.