Acute hypoxic pulmonary vasoconstriction in conscious dogs decreases renin and is unaffected by losartan

Abstract

Acute hypoxic pulmonary vasoconstriction (HPV) may be mediated by vasoactive peptides. We studied eight conscious, chronically tracheostomized dogs kept on a standardized dietary sodium intake. Normoxia (40 min) was followed by hypoxia (40 min, breathing 10% oxygen, arterial oxygen pressures 36 +/- 1 Torr) during both control (Con) and losartan experiments (Los; iv infusion of 100 microg. min-1. kg-1 losartan). During hypoxia, minute ventilation (by 0.9 l/min in Con, by 1.3 l/min in Los), cardiac output (by 0.36 l/min in Con, by 0.30 l/min in Los), heart rate (by 11 beats/min in Con, by 30 beats/min in Los), pulmonary artery pressure (by 9 mmHg in both protocols), and pulmonary vascular resistance (by 280 and 254 dyn. s. cm-5 in Con and Los, respectively) increased. Mean arterial pressure and systemic vascular resistance did not change. In Con, PRA decreased from 4.2 +/- 0.7 to 2.5 +/- 0.5 ng ANG I. ml-1. h-1, and plasma ANG II decreased from 11.9 +/- 3.0 to 8.2 +/- 2.1 pg/ml. The renin-angiotensin system is inhibited during acute hypoxia despite sympathetic activation. Under these conditions, ANG II AT1-receptor antagonism does not attenuate HPV.

Hypoxic Pulmonary Vasoconstriction

“…Acute hypoxia was reported to both increase (823,1089) and decrease (997) plasma renin activity in dogs. Hypoxia had no effect on conversion of ANG I to ANG II in endothelial cells (1874) or fetal lung allografts in hamster cheek pouch (1765), but decreased ACE activity in anesthetized or conscious dogs (997,1873) and isolated rabbit lungs (1628), possibly due to an HPV-induced decrease in endothelial surface area (1433). ANG I or ANG II increased normoxic pulmonary vasomotor tone and HPV in cats (1851), dogs (31), and rats (152, 1240, 1851), but not ferrets (1851).…”

“…Exogenous ANG II caused vasoconstriction in lungs of cats (1552), dogs (625,1405), humans (258), mice (494), pigs (1221), rabbits (2063), and rats (121, 566, 1240, 2039) as well as in isolated pulmonary arteries of dogs (1887) and rats (200,1652). Under normoxic conditions, some studies showed that ACE inhibition or angiotensin II receptor blockade reduced pulmonary vasomotor tone (259, 625, 1405), suggesting basal activation of the renin-angiotensin system; however, others failed to confirm these effects (720,823,959,997,1552).…”

“…Although an initial study in isolated rat lungs perfused with physiological salt solution concluded that enhancement of HPV by ANG II was specific for both HPV and ANG II (152), this was not confirmed by a subsequent study in the same preparation, which found that increases in normoxic pulmonary vasomotor tone, whether caused by ANG II or other interventions, enhanced vasoconstrictor responses to both hypoxia and KCl (1240). Antagonists of ACE or ANG II receptors did not prevent HPV in dogs (720,823,997), cats (1552), or isolated rat lungs (509, 1242), but attenuated HPV in humans (259, 958) and neonatal piglets (249). Although the explanation for these discrepancies is unknown, the data suggest that ANG II may sometimes facilitate HPV.…”

Lung Circulation

“…Exogenous ANG II causes pulmonary vasoconstriction in most species, both in isolated vessel and intact lung preparations (37,70,87,160,185,222,404,408,462,506,534,614,682). Some studies suggest that basal activation of the renin-angiotensin system and production of ANG II exerts a slight vasoconstrictor effect on the pulmonary circulation (222,462), although other studies failed to show an effect of ANG II blockade at baseline (246,276,323,335,506).…”

The Role of Angiotensin II Receptor-1 Blockade in the Hypoxic Pulmonary Vasoconstriction Response in Newborn Piglets

“…Cardiac output increases during acute hypoxic exposure in adult animal models and humans in order to maintain oxygen delivery at the peripheral tissues [14,15,28,29] . However, we have previously demonstrated that CO did not change significantly during acute hypoxia in healthy newborn piglets exposed to 14% O 2 [30] .…”