Inhalation of nebulized nitroglycerin, a nitric oxide donor, for the treatment of pulmonary hypertension induced by high pulmonary blood flow.
This study explores the effect and mechanisms of inhalation of nebulized nitroglycerin (Neb-NTG) on pulmonary hypertension induced by high pulmonary blood flow. An aortocaval shunt was produced in rats. Twelve weeks after the operation, rats started to inhale Neb-NTG. After 15 weeks, pulmonary and systemic hemodynamics as well as pathological changes were measured in all animals. Inhalation of Neb-NTG was able not only to markedly attenuate pulmonary artery pressure without impacting systolic pressure but also to ameliorate muscularization of small pulmonary arteries. The relaxation response of pulmonary artery ring to acetylcholine in shunt rats and Neb-NTG-treated rats was decreased. However, Neb-NTG did not impact the relaxation response of pulmonary artery ring to both nitroprusside and nitroglycerin (NTG). Neb-NTG successfully inhibited the increased expression of pulmonary artery smooth muscle cell (PASMC) proliferative cell nuclear antigen, collagen I, and collagen III, as well as pulmonary artery urotensin-II in shunt rats with high pulmonary blood flow. Neb-NTG selectively ameliorated pulmonary hypertension as well as pulmonary vascular structural remodeling induced by high pulmonary blood flow.
Puikuan
Kan
K
Department of Pediatrics, Peking University First Hospital, Xian Men Street No. 1, West District, Beijing, 100034, P.R. China.
Chunyu
Zhang
Z
Jin
Fan
F
Chaoshu
Tang
T
Junbao
Du
D
D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D005996:Nitroglycerin / Q000008:administration & dosage*; D011651:Pulmonary Artery / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D014579:Urotensins / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage*
D020030:Nitric Oxide Donors; D014579:Urotensins; D014665:Vasodilator Agents; C029677:urotensin II; D005996:Nitroglycerin