Analysis of the role of endothelial nitric oxide in regulating the tone and responses of pulmonary artery rings to drugs

The work presented here represents an examination of the effects of various drugs on the tone of vascular smooth muscle in isolated pulmonary artery rings mainly from Wistar rats and an investigation of contribution of endothelium- derived relaxing factor (EDRF, NO). The results obtained in these studies are summarised below: 1) The vasoconstrictors, 5-hydroxytryptamine (5-HT, 10-7 to 10-3M), phenylephrine (PHE, 10-9 to 10-4M), noradrenaline (NA, 10-10 to 10-6M), angiotensin II (Ang II, 10-11 to 10-7M) and the thromboxane A2 (TXA2) analogue, U46619 (10-9 to 10-6M), induced concentration-dependent contractions in main (MPA) and branch (BPA) pulmonary artery rings from Wistar rats. 2) Exposure of MPA and BPA rings for 30min or 1 hour to the concentration of 5-HT (10-4M), that produced the maximum response caused a marked desensitisation to 5-HT. 3) The endothelium-dependent vasorelaxants, ACh (10-9 to 3x10-6M) or carbachol (CARB, 10-8 to 10-4M) induced concentration-dependent relaxations in MPA rings and BPA rings, which had been precontracted with PHE (EC70, 1.2x10-7M). 4) The endothelium-independent vasorelaxant, sodium nitroprusside (SNP, 10-12 to 10-5M) induced concentration-dependent relaxations in MPA and BPA rings, which had been precontracted with PHE (EC70, 1.2x10-7M) or 5-HT (EC50, 10-5M). MPA rings, which had been precontracted with PHE, were more responsive than BPA rings to low concentrations of SNP (10-11M) and also to high concentrations of SNP (10-7 to 10-6M). 5) The purine adenine nucleotides, ATP and ADP induced concentration-dependent relaxations (10-8 to 10-5M) in MPA and BPA rings, which had been precontracted with PHE (10-7M). 6) Histamine (HIST, 10-6 to 10-3M) induced concentration-dependent relaxations in MPA and BPA rings, which had been precontracted with PHE (10-7M). 7) The beta-adrenoceptor agonist, isoproterenol (ISO, 10-10 to 10-5M), induced concentration-dependent relaxations in MPA and BP A rings precontracted with PHE (10-7M). 8) 5-HT (10-4 to 5x10-4M) induced concentration-dependent relaxations in MPA and BPA rings, which had been precontracted with PHE (EC75, 1.2x10-7M). 9) The muscarinic-receptor antagonist, atropine (AT, 10-8 to 5x10-6M) induced concentration-dependent relaxations in MPA and BPA rings, which had been precontracted with PHE (10-7M) or 5-HT (10-5M) but not with KCI 3x10-2M). 10) Electrical field stimulation (EFS) induced frequency-dependent contractions in MPA rings. 11) In MPA and BPA rings, which had been precontracted with PHE; pretreatment with standard solutions of cigarette smoke extract (CSE, 1ml, for 10-15min), depressed vasorelaxant responses to ACh (10-9 to 10-5M) but had no effect on relaxant responses to SNP (10-11 to 10-5M). 12) Noradrenaline (NA) and 5-hydroxytryptamine (5-HT) induced concentration-dependent contractions in MPA and BPA rings of sham operated and heart failure rabbits. There were no significant differences between responses of blood vessels from sham operated and EOF rabbits to these agonists. Acetylcholine (ACh) induced concentration-dependent relaxations in these rings from sham operated and HF rabbits. There were significant differences between the responses in BPA rings only at the lowest concentration of ACh (10-9M). (Abstract shortened by ProQuest.)