SUMMARYWe investigated the effects of catecholamines and sympathetic nerve stimulation in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow. Norepinephrine and nerve stimulation caused dose-and stimulus frequency-dependent increases in pulmonary vascular resistance. However, when pulmonary vascular tone was enhanced and a receptors blocked, norepinephrine and nerve stimulation caused dose-and frequency-dependent decreases in pulmonary vascular resistance. The decreases in pulmonary vascular resistance were blocked with propranolol and were of greater magnitude than were constrictor responses observed under basal conditions. Vasodilator responses to nerve stimulation were not modified by atropine. Epinephrine and isoproterenol had marked vasodilator activity in the pulmonary vascular bed when pulmonary vascular tone was elevated. When o receptors were blocked, isoproterenol and epinephrine had similar vasodilator activity, and when fi receptors were blocked, epinephrine and norepinephrine had marked vasoconstrictor activity. Selective /8-1 receptor antagonists had little effect on vasodilator responses to isoproterenol, whereas responses to this substance were blocked by propranolol. These results suggest the presence of a-and f}-2 adrenoreceptors in the feline pulmonary vascular bed and that both types of adrenergic receptors are innervated by the sympathetic nervous system. Circ Res 48: [407][408][409][410][411][412][413][414][415] 1981

SUMMARY. Responses to vagal stimulation and acetylcholine were investigated in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow and constant left atrial pressure. Under baseline conditions, electrical stimulation of vagal efferent fibers increases lobar arterial pressure. However, when vasoconstrictor tone was increased, a depressor response was unmasked. The pressor response under baseline conditions and the depressor response under enhanced tone conditions were blocked by phenoxybenzamine and atropine. These data suggest that, in the cat, the vagus is composed of efferent fibers from both the sympathetic and parasympathetic systems. After treatment with 6-hydroxydopamine to destroy the integrity of the sympathetic system, vagal stimulation caused significant frequency-dependent decreases in lobar arterial pressure when lobar vascular tone was increased by infusion of a stable prostaglandin endoperoxide analog or ventilatory hypoxia. Injections of acetylcholine also caused significant dose-related decreases in lobar arterial pressure when lobar vascular resistance was elevated. Depressor responses to vagal stimulation and acetylcholine in 6-hydroxydopamine-treated animals were blocked by atropine and enhanced by physosrigmine. Decreases in lobar arterial pressure in response to vagal stimulation in 6-hydroxydopamine-treated animals with enhanced tone were blocked by hexamethonium, whereas responses to injected acetylcholine were not altered by the ganglionic blocking agent. Decreases in lobar arterial pressure in response to vagal stimulation and acetylcholine were similar when the lung was ventilated and when the left lower lobe bronchus was obstructed. In addition, responses to vagal stimulation were similar when systemic arterial pressure was decreased to the level of pressure in the perfused lobar artery. Responses to acetylcholine were not altered after treatment with 5,8,11,14-eicosatetraynoic acid, a lipoxygenase inhibitor. The present data suggest that the feline pulmonary vascular bed is functionally innervated by cholinergic nerves and that vagal stimulation dilates the pulmonary vascular bed by releasing acetylcholine which acts on muscarinic receptors in pulmonary vessels. (Circ Res 53: 86-95, 1983)

We investigated the effects of vasoactive intestinal peptide (VIP) in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow when pulmonary vascular tone was at base-line levels and when vascular resistance was elevated. Under base-line conditions, VIP caused small but significant reductions in lobar arterial pressure without affecting left atrial pressure. Decreases in lobar arterial pressure in response to VIP were greater and were dose related when lobar vascular resistance was increased by intralobar infusion of U 46619, a stable prostaglandin endoperoxide analogue. Acetylcholine and isoproterenol also caused significant decreases in lobar arterial pressure under base-line conditions, and responses to these agents were enhanced when lobar vascular tone was elevated. Moreover, when doses of these agents are expressed in nanomoles, acetylcholine and isoproterenol were more potent than VIP in decreasing lobar arterial pressure. Responses to VIP were longer in duration with a slower onset than were responses to acetylcholine or isoproterenol. Pulmonary vasodilator responses to VIP were unchanged by indomethacin, atropine, or propranolol. The present data demonstrate that VIP has vasodilator activity in the pulmonary vascular bed and that responses are dependent on the existing level of vasoconstrictor tone. These studies indicate that this peptide is less potent than acetylcholine or isoproterenol in dilating the feline pulmonary vascular bed and that responses to VIP are not dependent on a muscarinic or beta-adrenergic mechanism or release of a dilator prostaglandin.

A B S T R A C T. The objective of this study was to determine the direct actions of nitroprusside and nitroglycerin on the pulmonary vascular bed in the intactchest dog. These widely used nitrogen oxide-containing vasodilator agents decreased pulmonary arterial pressure and increased cardiac output without altering left atrial pressure. Reductions in pulmonary arterial pressure and pulmonary vascular resistance were small under resting conditions, but were enhanced when pulmonary vascular tone was elevated by infusion of a stable prostaglandin analog that increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In studies in which pulmonary blood flow to the left lower lobe was maintained constant, nitroprusside and nitroglycerin caused small but significant reductions in lobar arterial and small-vein pressures without significantly affecting left atrial pressure. With constant blood flow, lobar vascular pressures that were reduced in response to the vasodilators were more greatly reduced when lobar vascular resistance was increased by infusion of the prostaglandin analog or serotonin. However, when lobar vascular pressures were elevated by passive obstruction of lobar venous outflow, vasodilator responses to nitroprusside and nitroglycerin were not enhanced. These data suggest that nitroprusside and nitroglycerin decrease pulmonary vascular resistance by dilating intrapulmonary veins and upstream segments. These responses were minimal under control conditions but were enhanced when vascular tone was increased. This vasodilator action is independent of passive factors such as changes in pulmonary blood flow or left atrial pressure and is not secondary to an effect of these agents on the systemic circulation. Pulmonary vasodilator responses to nitroprusside and nitroglycerin were, however, found to be dependent on the existing level of vasomotor tone in the pulmonary vascular bed.

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