Effect of bronchospasm on hypoxic pulmonary vasoconstriction (HPV) in perfused cat lungs

Abstract

It has been believed that autonomic nerve plays little role in HPV. However, these studies were done in the conditions with normal bronchial tone. Little has been known about the role of autonomic nerve on HPV during broncho-spasm as in the case with bronchial asthma, in which autonomic nerves are involved in pathogenesis and the altered tone of autonomic nerve may affect pulmonary circulation. To clarify the role of autonomic nerves on HPV when there is bronchospasm, we induced hypoxia while provoking bronchospasm by intratracheal administration of histamine or acetylcholine in isolated cat lungs (n=36) perfused with diluted autologous blood (Ht=l 0%). We used 30% 02 and 5% CO2 for noormoxia and 2% 02 and 5% CO2 for hypoxia. Hexamethonium (C6) as a ganglion blockaer, tetrodotoxin (TTX) as a blockade of nerve conduction, atropine a muscarinic receptor antagonist, and also selective or non-selective adrenergic inhibitors (8: propranolol, 131 ;acebutolol, metoprolol, 13-2;butoxamine, alpha; phentolamine, alpha-1 ; prazosin, alpha-2; yohimbin) were administered before induction of bronchospasm following control HPV. C6 and TTX did not affect parameters of pulmonary circulation when HPV was not accompanied by bronchospasm or when bronchospasm was induced during normoxia. Nevertheless, these agents attenuated HPV when there was bronchospasm. Atropine almost completely abolished HPV during bronchospasm. Beta and selective 13-2 inhibitors also completely abolished HPV during bronchospasm. Alpha blockades did not affect HPV even when there was bronchospasm. We conclude that autonomic nerves, especially vagal nerves and 13 adrenergic nerve play a crucial role in HPV when it occured during bronchospasm. These finding may indicate that many sympathetic agonist and anti-cholinergic drugs, used in the treatment of bronchial asthma, may affect ventilation-perfusion matching.