thiourea and Vascular-Diseases

To study the value of indexes of endothelial cell function in experimentally induced pulmonary microvascular injury, lung damage was produced in anesthetized dogs by intravenous injection of oleic acid (OA; n = 6), alpha-naphthylthiourea (ANTU; n = 5), or phorbol myristate acetate (PMA; n = 6). Angiotensin-converting enzyme (ACE) activity in serum and simultaneous measurements of serotonin (SER) and propranolol (PROP) pulmonary extraction along with several physiologic parameters were determined and compared with those obtained in a control group (n = 5) before and then at 2-h intervals for 8 h after administration of the toxic agent. ACE activity in serum showed a sustained and significant increase in the PMA and OA groups throughout the whole study period, whereas it decreased significantly at 4 h in the ANTU group. SER pulmonary uptake decreased significantly, but slightly, only in the PMA group at 8 h (-5%). At 6 and 8 h respectively, PROP extraction dropped significantly in the PMA (-11 and -13%) and OA (-13 and -19%) groups. This decrease in PROP extraction was likely to result from physiologic changes due to the development of pulmonary edema as suggested by the correlation between the changes in amine uptake and those affecting pulmonary artery pressure and total static respiratory compliance. The lack of effects on SER uptake by the lungs under these experimental conditions indicate that dissociation exists between metabolic dysfunction of pulmonary endothelial cells and fluid leakage.

Topics: Anesthesia; Animals; Blood Pressure; Dogs; Endothelium, Vascular; Lung; Lung Diseases; Microcirculation; Oleic Acid; Oleic Acids; Peptidyl-Dipeptidase A; Propranolol; Pulmonary Circulation; Serotonin; Tetradecanoylphorbol Acetate; Thiourea; Vascular Diseases; Vascular Resistance

Recent work with isolated blood vessels has emphasized the importance of intact endothelium when the relaxation of vascular smooth muscle is induced by acetylcholine (ACh). However, the physiologic significance of this endothelial-dependent ACh response in a complete organ circulation is unclear. We questioned whether diminished ACh vasodilation would result from damage of lung vascular endothelium and whether this response could be used as an indication of endothelial injury. We therefore induced pulmonary endothelial cell injury in one rat model by repeated injections of alpha-naphthyl thiourea (ANTU) and in a second rat model by exposing rats for 52 h to 100% oxygen at a barometric pressure of 760 torr (hyperoxia). Rats injected with Tween 80, the solvent for ANTU, or exposed to ambient Denver air served as the respective control animals. The isolated lungs of these rats were perfused with a recirculating cell- and plasma-free, physiological salt solution to study the effect of ACh or NaCl infusion on pulmonary perfusion pressure and vascular responsiveness. ANTU-treated rats demonstrated an intact vasodilatory response after ACh infusion when compared with the solvent control animals. The immediate pulmonary vasodilation after ACh infusion was slightly enhanced in the hyperoxic rat lung when compared with the rats exposed to ambient air, but there was no difference between these groups in the prolonged depression of vascular responsiveness to hypoxia or angiotensin II. Thus, in both models of lung endothelial cell injury, the pulmonary vascular responses to ACh were intact.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetylcholine; Acute Disease; Animals; Chronic Disease; In Vitro Techniques; Lung Diseases; Male; Microbial Collagenase; Microscopy, Electron; Oxygen; Perfusion; Pulmonary Circulation; Pulmonary Edema; Rats; Rats, Inbred Strains; Thiourea; Vascular Diseases; Vasodilation