Abstract-␤ 2 -Adrenoceptors are important modulators of vascular tone, particularly in the pulmonary circulation. Because neurohormonal activation occurs in pulmonary arterial hypertension, we have investigated the effect of different adrenergic vasoactive substances on tone regulation in large and small pulmonary arteries, as well as in systemic vessels of mice. We found that the ␤ 2 -adrenoceptor antagonist ICI 118,551 (ICI) evoked a decrease of vascular tone in large pulmonary arteries and reduced the sensitivity of pulmonary arteries toward different contracting agents, eg, norepinephrine, serotonin, or endothelin. ICI proved to act specifically on pulmonary vessels, because it shifted the dose-response curve of norepinephrine to the right in pulmonary arteries, whereas there was no effect in the aorta. Pharmacological experiments proved that the right shift of the norepinephrine dose-response curve by ICI was mediated via a ␤ 2 -adrenoceptor/G i/o protein-dependent pathway enhancing NO production in the endothelium; these results were corroborated in ␤-adrenoceptor and endothelial NO synthase knockout mice where ICI had no effect. ICI increased vascular lumen diameter in lung sections and reduced pulmonary arterial pressure under normoxia and under hypoxia in the isolated perfused lung model. These effects were found to be physiologically relevant, because ICI specifically decreased pulmonary but not systemic blood pressure in vivo. Thus, the ␤ 2 -adrenoceptor antagonist ICI is a pulmonary arterial-specific vasorelaxant and, therefore, a potentially interesting novel therapeutic agent for the treatment of pulmonary arterial hypertension. proteins and have an important vasorelaxing function in the systemic and pulmonary circuits. All of the isoforms that are known so far (␤ 1 -, ␤ 2 -, ␤ 3 , and low-affinity-state ␤ 1 -AR) have been identified in pulmonary vessels, 1-3 with the ␤ 2 -AR being the most potent for vasorelaxation. 4 The pulmonary arteries (PAs) are important therapeutic targets, because pulmonary arterial hypertension often occurs after cardiac surgery in children 5 but also in adults and can result in life-threatening right heart failure. Therefore, specific and fast-acting vasodilators for PAs are urgently needed. However, most drug treatment regimens also strongly decrease vascular tone in the systemic circuit, leading to hypotension.Other than ␤-AR agonists, ␤-blockers were also reported to show promising results in the treatment of pulmonary arterial hypertension, which was not caused by left ventricular disorders. 6 In systemic arteries, it has been demonstrated that thirdgeneration ␤-blockers can directly induce vasodilation via NO release from the endothelium 7 and thereby positively affect the afterload. The aim of our study was to identify pulmonary specific vasorelaxants, and we have, therefore, investigated the impact of different ␤-adrenergic mediators on vascular tone in the pulmonary and systemic circulations of mouse. We have identified ICI 118,551 (ICI), a ␤-blocker with antago...

Real-time 3D using a matrix transducer is a feasible, reliable and valid method for volume determination in the fetus beyond 19 weeks of gestation. If compared to 2D, real-time 3D echocardiography provides improved accuracy of cardiac volumetry, decreases intraobserver and interobserver variability and is a promising tool for the accurate assessment of cardiac size and function.

This article discusses the physiology of altitude exposure, the current state of knowledge in children and adults with PAH, and provides a balanced overview of the latest recommendations for safe travel in pediatric PAH. Cardiopulmonary response to high altitudeWith increasing altitude, barometric pressure, air temperature and air humidity decrease. As a consequence, the inspired oxygen partial pressure and the alveolar oxygen pressure decline in an exponential fashion (1-3) (Figure 1). At sea level, oxygen constitutes 21% of inspired air, which

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Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse. This effect was found to be independent of β ARs and the endothelium but was determined by the type of the preconstrictor. Vasodilation by β AR agonists occurred after pretreatment of pulmonary arteries with phenylephrine and serotonin, both agonists of α ARs, but was absent after preconstriction with the thromboxane analog U46619. These data indicated α-adrenolytic activity of β AR agonists, which was confirmed by a right shift of the phenylephrine dose-response curve by TER. This effect was physiologically relevant because TER also relaxed small intrapulmonary arteries in lung slices and diminished pulmonary arterial pressure in an isolated perfused lung model under normoxia and hypoxia. Finally, TER applied as an aerosol also selectively decreased pulmonary arterial pressure without effects on systemic blood pressure and heart rate in mouse in vivo. Thus, β AR agonists display α-adrenolytic activity in pulmonary arteries ex vivo and in vivo, and may provide a novel option to reduce pulmonary arterial pressure in pulmonary hypertension.-Neumann, V., Knies, R., Seidinger, A., Simon, A., Lorenz, K., Matthey, M., Breuer, J., Wenzel, D. The β agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.