Response of Intra-acinar Pulmonary Microvessels to Hypoxia, Hypercapnic Acidosis, and Isocapnic Acidosis

Abstract

To elucidate the differential reactivity of pulmonary microvessels in the acini to hypoxia, excessive CO2, and increased H+, we investigated changes in the diameter of precapillary arterioles, postcapillary venules, and capillaries in isolated rat lungs on exposure to normocapnic hypoxia (2% O2), normoxic hypercapnia (15% CO2), and isocapnic acidosis (0.01 mol/L HCl). Microvascular diameters were precisely examined using a real-time confocal laser scanning luminescence microscope coupled to a high-sensitivity camera with an image intensifier. Measurements were made under conditions with and without indomethacin or N(omega)-nitro-L-arginine methyl ester to assess the importance of vasoactive substances produced by cyclooxygenase (COX) or NO synthase (NOS) as it relates to the reactivity of pulmonary microvessels to physiological stimuli. We found that acute hypoxia contracted precapillary arterioles that had diameters of 20 to 30 microm but did not constrict postcapillary venules of similar size. COX- and NOS-related vasoactive substances did not modulate hypoxia-elicited arteriolar constriction. Hypercapnia induced a distinct venular dilatation closely associated with vasodilators produced by COX but not by NOS. Arterioles were appreciably constricted in isocapnic acidosis when NOS, but not COX, was suppressed, whereas venules showed no constrictive response even when both enzymes were inhibited. Capillaries were neither constricted nor dilated under any experimental conditions. These findings suggest that reactivity to hypoxia, CO2, and H+ is not qualitatively similar among intra-acinar microvessels, in which COX- and NOS-associated vasoactive substances function differently.

NOS and COX isoforms and abnormal microvessel responses to CO2 and H+ in hyperoxia-injured lungs

“…In another study, it was found that this hypercapnia-associated venule dilatation in intact lungs is significantly attenuated in hyperoxia-injured lungs due to inhibition of COX activity by excessive NO [7]. However, these previous studies did not determine the relative contributions of COX (COX-1 and COX-2) and nitric oxide synthase (NOS) isoforms (endothelial constitutive (ecNOS) and inducible NOS (iNOS)) to the abnormal acinar microvessel response to HA [4,7]. Furthermore, they did not partition the abnormal microvessel response to HA into that caused by a high carbon dioxide concentration and that by a high hydrogen ion concentration, both of which occur under conditions of HA.…”

“…The vascular reactivity of pulmonary microvessels, especially acinar microvessels, in response to acidosis induced by either alveolar hypercapnia (hypercapnic acidosis (HA)) or metabolic disturbance (isocapnic acidosis (IA)) is one of the major modulators regulating the distribution of pulmonary blood flow [1][2][3][4]. An exact knowledge of acinar microvessel behaviour in acidosis is absolutely necessary when treating patients with diseased lungs using controlled ventilation with permissive hypercapnia, which has increasingly assumed an important place in managing acute lung injury [5,6].…”

“…An exact knowledge of acinar microvessel behaviour in acidosis is absolutely necessary when treating patients with diseased lungs using controlled ventilation with permissive hypercapnia, which has increasingly assumed an important place in managing acute lung injury [5,6]. In a previous study, it was demonstrated that HA induces distinct venule dilatation closely associated with vasodilating prostaglandins generated by cyclo-oxygenase (COX), but not by nitric oxide (NO), in intact rat lung [4]. In another study, it was found that this hypercapnia-associated venule dilatation in intact lungs is significantly attenuated in hyperoxia-injured lungs due to inhibition of COX activity by excessive NO [7].…”

Videomorphometric Analysis of Hypoxic Pulmonary Vasoconstriction of Intra-pulmonary Arteries Using Murine Precision Cut Lung Slices

“…Our data on the extent of HPV matches well to results obtained with a different experimental approach. Yamaguchi et al have applied isolated rat lungs to examine microvessels with diameter of 20-30 µm by real-time confocal laser scanning luminescence microscopy coupled to a high-sensitivity camera with an image intensifier 10 . They observed a mean reduction in diameter of 2.7 µm after exposure of the lungs to hypoxia.…”

“…The intra-acinar artery feeding an individual pulmonary acinus with blood represents a partially muscular segment 6 . Likewise, the pulmonary arterial system does not represent a uniform structure regarding the hypoxic response but exhibits marked regional diversity 9,10 . For instance, in proximal pulmonary arteries isolated from rat lungs hypoxia induces a biphasic response, displaying an initial rapid contraction of short duration which -after incomplete relaxation -is followed by a second slow but sustained contraction 11 .…”