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ilová3Depts of 1 Physiology and 3 Pathology, Charles University Second Medical School, and 2 Centre for Experimental Cardiovascular Research, Prague, Czech Republic
CORRESPONDENCE: V. Hampl, Dept of Physiology, Charles University Second Medical School, Plzenska 130/221, 150 00 Prague 5, Czech Republic. Fax: 420 257210995. E-mail: vaclav.hampl@lfmotol.cuni.cz
Keywords: antioxidants, hormones, hypertension, large-conductance calcium-activated potassium channel, potassium channels, pulmonary
Received: September 12, 2002
Accepted November 20, 2002
This study was supported by the grant agency of the Czech Republic, grant nos. 306/97/0854, 305/97/S070 and 305/00/1432.
Pathogenesis of pulmonary hypertension includes vascular smooth muscle cell membrane depolarisation and consequent calcium influx. Usually, calcium-gated potassium channels are activated under such conditions and repolarise the membrane. However, in pulmonary hypertension they are downregulated. The authors hypothesised that pharmacological augmentation of these channels would reduce pulmonary hypertension.
Dehydroepiandrosterone sulphate (DHEA-S, 0.1 mg·mL–1), a recently characterised activator of calcium-gated potassium channels, was given to rats in drinking water.
Pulmonary arterial blood pressure, increased by 4 weeks of hypoxia (from 15±0.2 to 29.4±2.5 mmHg), was selectively attenuated in rats treated with DHEA-S for the whole duration of the hypoxic exposure (23.9±0.9 mmHg) and in rats given DHEA-S only after pulmonary hypertension had fully developed (last 2 weeks of hypoxia; 24.4±1.4 mmHg). Pulmonary vascular remodelling and right ventricular hypertrophy associated with pulmonary hypertension were also reduced by DHEA-S. Cardiac index and systemic arterial blood pressure did not differ among the groups.
The authors conclude that treatment with an activator of calcium-gated potassium channels, dehydroepiandrosterone sulphate, known to be well tolerated by humans, reduces hypoxic pulmonary hypertension in rats.
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