Pulmonary vascular tone is increased by a voltage-dependent calcium channel potentiator

The mechanism of hypoxia-induced pulmonary vasoconstriction remains unknown. To explore the possible dependence of the hypoxic response on voltage-activated calcium (Ca²⁺) channels, the effects of BAY K 8644 (BAY), a voltage-dependent Ca²⁺ channel potentiator, were observed on the pulmonary vascular response to hypoxia of both the intact anesthetized dog and the perfused isolated rat lung. In six rat lungs given BAY (1 x 10^-6 M), hypoxia increased mean pulmonary arterial pressure (Ppa) to 30.5 ± 1.7 (SEM) Torr compared with 14.8 ± 1.2 Torr for six untreated rat lungs (P < 0.01). After nifedipine, the maximum Ppa during hypoxia fell 14.1 ± 2.4 Torr from the previous hypoxic challenge in the BAY-stimulated rats (P < 0.01). BAY (1.2 x 10^-7 mol/kg) given during normoxia in seven dogs increased pulmonary vascular resistance 2.5 ± 0.3 to 5.0 ± 1.2 Torr·l^-1·min (P < 0.05), and systemic vascular resistance 55 ± 4.9 to 126 ± 20.7 Torr·l^-1·min (P < 0.05). Systemic mean arterial pressure rose 68 Torr, whereas Ppa remained unchanged. Administration of BAY during hypoxia produced an increase in Ppa: 28 ± 1.5 to 33 ± 1.9 Torr (P < 0.05). Thus BAY, a Ca²⁺ channel potentiator, enhances the hypoxic pulmonary response in vitro and in vivo. This, together with the effect of nifedipine on BAY potentiation, suggests that increased Ca²⁺ channel activity may be important in the mechanism of hypoxic pulmonary vasoconstriction.