Mechanisms controlling vascular tone in pulmonary arterial hypertension: implications for vasodilator therapy.
Pulmonary vasoconstriction is believed to be an early component of pulmonary arterial hypertension. Intracellular calcium concentration ([Ca(2+)](i)) is a major trigger for pulmonary vasoconstriction; however, it is now well known that contractions and relaxations may also be elicited through Ca(2+)-independent mechanisms. A variety of intracellular protein kinases and cyclic nucleotides have been identified as key determinants in controlling pulmonary vascular tone. Herein, we provide an overview of the main signaling pathways, which include protein kinase C, Rho kinases and cyclic nucleotides (cAMP and cGMP). This review also focuses on the role of store-operated Ca(2+) channels and voltage-gated K(+) channels, which are currently considered especially attractive in the pulmonary circulation and may represent new targets in the treatment of pulmonary arterial hypertension.
Cogolludo
Angel
A
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain. acogolludo@ift.csic.es
Moreno
Laura
L
Villamor
Eduardo
E
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011652:Pulmonary Circulation; D014661:Vasoconstriction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D009569:Nitric Oxide; D000242:Cyclic AMP; D011493:Protein Kinase C; D020741:rho GTP-Binding Proteins; D006152:Cyclic GMP