In this episode, we dive into the early therapies and how our understanding of vascular physiology drastically changed the management of pulmonary hypertension.

• Intro 0:12
• In this episode 0:18
• Recap of part 1 & 2 0:31
• What part 3 is about 2:31
• WHO conference in 1975: Treating pulmonary hypertension 3:48
• The Discovery of Non-Steroidal Anti-inflammatory Drugs (NSAIDs), Part 1 5:20
• Epoprostenol 6:18
• Prostacyclin 10:37
• Endothelin antagonists 11:41
• Phosphodiesterase type 5 (PDE5) inhibitors 14:08
• Interaction of nerves and blood vessels 15:06
• The Soups VS the Sparks 17:36
• A dreamed experiment 19:06
• Acetylcholine 23:23
• Enter "the calabar bean" 24:45
• Acetylcholine and vasodilation: 1976 26:01
• Rabbit aorta 27:45
• Nitric oxide 29:38
• Why are we using nitric oxide to treat pulmonary hypertension? 31:31
• Tachyphylaxis 33:48
• TNT factories 35:09
• Nitrous oxide and tachyphylaxis 36:52
• Pfizer in the 1980s 38:06
• Understanding the trigger of pulmonary hypertension 40:53
• PDE5 and nitric oxide and pulmonary hypertension 43:07
• The end of the ripping yarns 44:20
• Coming up in part 4 46:17
• Thanks for listening 47:29

We'd love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.

References: Bernard C. C R Soc Biol. 1851;3:163-164. Furchgott RF, et al. Nature. 1980;doi:10.1038/288373a0. Galiè N, et al. N Engl J Med. 2005;doi:10.1056/NEJMoa050010. Ghofrani HA, et al. Nat Rev Drug Discov. 2006;doi:10.1038/nrd2030. Giordano D, et al. Biochim Biophys Acta. 2001;doi:10.1016/s0167-4889(01)00086-6. Guthrie F. Q J Chem Soc. 1859;doi:10.1039/QJ8591100245. Higenbottam T, et al. Lancet. 1984;doi:10.1016/s0140-6736(84)91452-1. Marsh N, et al. Clin Exp Pharmacol Physiol. 2000;doi:10.1046/j.1440-1681.2000.03240.x. Montastruc JL, et al. Clin Auton Res. 1996;doi:10.1007/BF02281906. Nejad SH, et al. Future Cardiol. 2024;doi:10.1080/14796678.2024.2367390. Tansey EM. C R Biol. 2006;doi:10.10116/j.crvi.2006.03.012. Warren JV. Trans Am Clin Climatol Assoc. 1988;99:10-6.

Disclosures: Brown reports no relevant financial disclosures.