Chronic hypertension impairs flow-induced vasodilation and augments the myogenic response in fetal lung.
We hypothesized that altered vasoreactivity in perinatal pulmonary hypertension (PH) is characterized by abnormal responses to hemodynamic stress, including the loss of flow-induced vasodilation and an augmented myogenic response. Therefore, we studied the acute hemodynamic effects of brief compression of the ductus arteriosus (DA) in control fetal lambs and in lambs during exposure to chronic PH. In both groups, acute DA compression decreased pulmonary vascular resistance (PVR) by 20% at baseline (day 0). After 2 days of hypertension, acute DA compression paradoxically increased PVR by 50% in PH lambs, whereas PVR decreased by 25% in controls. During the 8-day study period, PVR increased during acute DA compression in PH lambs, whereas acute DA compression continued to cause vasodilation in controls. Brief treatment with the nitric oxide (NO) synthase inhibitor nitro-L-arginine (L-NA) increased basal PVR in control but not PH lambs, suggesting decreased NO production in PH lambs. Chronic hypertension increased the myogenic response after L-NA in PH lambs, whereas the myogenic response remained unchanged in controls. The myogenic response was inhibited by nifedipine in PH lambs, suggesting that the myogenic response is dependent upon the influx of extracellular calcium. We conclude that chronic PH impairs flow-induced vasodilation and increases the myogenic response in fetal lung. We speculate that decreased NO signaling and an augmented myogenic response contributes to abnormal vasoreactivity in PH.
Storme
Laurent
L
Department of Neonatology, CHRU de Lille, France.
Parker
Thomas A
TA
Kinsella
John P
JP
Rairigh
Robyn L
RL
Abman
Steven H
SH
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002908:Chronic Disease; D004373:Ductus Arteriosus / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008168:Lung / Q000196:embryology*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011312:Pressure; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012756:Sheep; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D009543:Nifedipine