Effects of alpha adrenergic blockade and tissue catecholamine depletion on pulmonary vascular response to hypoxia

Abstract

A B S T R A C T The highly reactive pulmonary vascular bed of the neonatal calf was utilized to determine whether the hypoxic pulmonary pressor response is modified by a-adrenergic blockade with phenoxybenzamine (Group A) or by tissue catecholamine depletion with reserpine (Group B). In addition, in Group A, the effects of hypoxia on the pulmonary circulation were compared and contrasted with those of l-norepinephrine (a-receptor stimulator) and isoproterenol (,8-receptor stimulator).In Group A, changes in pulmonary vascular resistance were calculated from measurements of appropriate pressures and of pulmonary blood flow (electromagnetic flowmeter). The increase in pulmonary vascular resistance produced by hypoxia was not diminished by a-adrenergic blockade. However, blockade abolished the pulmonary vasoconstrictor effect of norepinephrine. During hypoxic pulmonary vasoconstriction, the administration of either norepinephrine or isoproterenol lowered the pulmonary vascular resistance both before and after a-blockade. 25 September 1967. sels secondary to an increased pulmonary blood flow.The pulmonary vascular response to hypoxia in the reserpinized calves (Group B) was tested under three circumstances: (1) in the awake animal, (2) in the anesthetized animal prepared in the same way as those in Group A, and (3) during constant flow perfusion of the left lower lobe pulmonary artery. From these studies it was concluded that tissue catecholamine depletion did not diminish the pulmonary vascular response to hypoxia.Thus, neither a-adrenergic blockade nor tissue catecholamine depletion prevents the hypoxic pulmonary pressor response. Furthermore, a-blockade prevents the pulmonary vasoconstrictor response to norepinephrine but not to hypoxia. Therefore it is concluded that hypoxic pulmonary vasoconstriction is not mediated through adrenergic receptor stimulation or release of endogenous catecholamines.

The Effect of Dexmedetomidine on Oxygenation and Intrapulmonary Shunt during One Lung Ventilation

“…The findings of a 1968 study by Silove and Grover demonstrated that an α-adrenergic blockade abolished the pulmonary vasoconstrictor responding to noradrenaline but not to hypoxia [18]. That is, hypoxiainduced pulmonary vasoconstriction cannot be impaired by sympathetic blockade.…”

Purinoceptors in the pulmonary circulation of the rat and their role in hypoxic vasoconstriction

“…It has been suggested that venoarterial or alveolarvascular reflexes confined to the lungs may be important in HPV (Fishman, 1976). Studies of HPV investigating the role of the autonomic nervous system have commonly used conventional antagonists of the parasympathetic and sympathetic components (Silove & Grover, 1968;Lewis, 1976). Burnstock (1972a) has proposed the 'purinergic hypothesis' that a purine nucleotide, probably ATP, is the principal transmitter released from nonadrenergic, noncholinergic 'purinergic' nerves.…”

Effect of isoproterenol on regional pulmonary perfusion and its blockade by propranolol.

“…We could not, however, confirm their findings; regional pulmonary perfusion responses after fl-blocking were similar to those during the control period, but (-blocking did prevent the effect of isoproterenol from relieving the regional hypoxic vasoconstriction. Silove and Grover (1968) stated that hypoxic vasoconstriction is not mediated through adrenergic receptor stimulation because the increase in pulmonary vascular resistance induced by hypoxia was not diminished by a-blockade. Malik and Kidd (1973) stated that the pulmonary vascular response to hypoxia in the intact dog is not under sympathetic control, and that the response to hypoxia is a local one.…”