Effect of angiotensin on hypoxic pulmonary vasoconstriction in isolated dog lung

Abstract

The effects of infused angiotensin on hypoxic pulmonary vasoconstriction in blood-perfused isolated dog lungs were studied. By using a double-perfusion system we were able to perfuse the right and left lungs separately in the same animal; one lung was used as control and the other lung was experimentally modified. The vasoconstrictive response to hypoxia decreased with time in the isolated lung preparations. The infusion of either angiotensin I or angiotensin II (1.2-5.8 mug/min) caused a threefold increase in the vasoconstrictive response to hypoxia over control levels. A second hypoxic period during the infusion usually yielded a diminished response, suggesting further degeneration of the response irreversible with angiotensin. It was concluded that angiotensin I or angiotensin II temporarily enhances hypoxic pulmonary vasoconstriction in isolated dog lungs.

Lisinopril Attenuates Acute Hypoxic Pulmonary Vasoconstriction in Humans

“…ANG II has been shown to play a vital facilitatory role in producing HPV in the rat 11 and appears to potentiate acute HPV in dogs. 12 In addition, treatment with an angiotensin-converting enzyme (ACE) inhibitor has been shown to attenuate the cardiopulmonary remodeling and pulmonary h~erten sion associated with chronic hypoxia in rats. 1 To our lmowledge, however, the nature of this interplay in the human pulmonary vasculature has not been studied.…”

Angiotensin 11 Receptor Blockade and Effects on Pulmonary Hemodynamics and Hypoxic Pulmonary Vasoconstriction in Humans

“…In vitro studies have shown that ANG II facil¬ itates HPV in the rat and potentiates this response in dogs. 8,9 Furthermore, the use of angiotensin-eonverting enzyme (ACE)-inhibitors in chronically hypoxic rats has been shown to attenuate the development of pulmonary hypertension.10 Studies in humans are rare, although recent data have shown that pretreatment with the long-acting ACE inhibitor lisinopril blunts acute HPV in normal volunteers compared to placebo.11 The effect of ACE inhibition could in theory be due to lowering levels of ANG II (a vasoconstrictor) or augmenting levels of bradykinin (a vasodilator) by suppressing the activity of kininase II, which normally contributes to the degra¬ dation of kinins.12…”

Restoration of Hypoxic Pulmonary Vasoconstriction following Normoxia in Isolated Dog Lungs Occurs in the Presence but Not in the Absence of Prostaglandin Synthesis Inhibitors

“…A special divider [2] was tied into the left at rium to separate the pulmonary venous return of one lung from that of the other. These procedures sepa rated the pulmonary circulations of the two lungs from one another.…”

“…Autologous blood was used to perfuse each lung with approximately 500 ml. Further details of these methods are available [2,3). Meanwhile, a double-lumen canine endotracheal tube was advanced to the carina to separate ventila tion of one lung from that of the other.…”

“…Alveolar hypoxia can produce pulmon ary vasoconstriction in isolated dog lungs [1][2][3]; this hypoxic pulmonary vasocon striction (HPV) can progressively dimin ish and reach a minimum within 45 min of the onset of perfusion [1][2][3]. Such a reduc tion in HPV can be reversed by prosta glandin (PG) synthesis inhibitors [3], but the precise factors that lead to this PG-de pendent reduction are unknown.…”