From the discovery of a mysterious blood-pressure–lowering effect in the venom of a Brazilian pit viper to the development of the first ACE inhibitor, we trace how scientists transformed a deadly toxin into lifesaving medicine. We follow the work that identified bradykinin-potentiating peptides in snake venom and revealed that angiotensin-converting enzyme could be blocked—leading to the creation of captopril and later drugs such as enalapril and lisinopril. Along the way, landmark experiments and clinical trials showed that ACE inhibitors do far more than lower blood pressure, reshaping the treatment of heart failure and chronic kidney disease by targeting maladaptive activation of the renin–angiotensin–aldosterone system.

• (00:00:00) - ACE Inhibitor Story Continues: Shutting off RAAS
• (00:01:00) - Recap: The RAAS Refresher
• (00:02:36) - Venom Mystery : Why Pit Viper Bites Cause Hypotension
• (00:05:02) - Venom and the ACE Connection: John Vane's Lab
• (00:06:20) - Interview With a Pit Viper: Snake’s Take on Pharma
• (00:09:18) - Venom Into Medicine: Turning Raw Venom into a Drug
• (00:10:04) - Captopril: The First ACE Inhibitor
• (00:11:04) - Better ACE Inhibitors: Captopril to Enalapril to Lisinopril
• (00:12:35) - Maladaptive RAAS Activation: Heart Failure Activates Renin
• (00:19:36) - Maladaptive RAAS Activation: Kidney Failure Activates Renin
• (00:24:24) - Episode Conclusion: ACE Inhibitors Transform Cardiorenal Medicine

From grinding up kidneys and injecting the extracts into animals to the famous Goldblatt clamp experiment, we trace decades of bold science that uncovered the body's most elaborate blood pressure system piece by piece. In part one of a two-part story, we follow the kidney's rise from simple filter to master regulator — through the discovery of renin, the bitter 17-year naming rivalry between Buenos Aires and Cleveland, and the identification of the enzyme that activates it all. Along the way, we encounter a Brazilian pit viper whose venom holds a molecular clue to one of modern medicine's greatest breakthroughs.

• (00:00:00) - ACE Inhibitors: A Two-Part Story Begins
• (00:01:00) - Catching Up: Hypertension, Early Treatments, and Accidental Drugs
• (00:02:35) - What Is an ACE Inhibitor?
• (00:03:27) - Step-by-Step RAAS: Renin → Angiotensin → Aldosterone
• (00:05:43) - Enter the Brazilian Pit Viper: Venom and Hypotension
• (00:07:45) - Dr. Richard Bright and the Kidney–Heart Connection
• (00:09:13) - Tigerstedt and the Discovery of Renin
• (00:10:27) - Wild Inspiration: Brown-Séquard’s Influence
• (00:11:36) - Rabbit Kidney Extracts and a Pressor Substance
• (00:13:52) - Goldblatt’s Clip: Renal Ischemia Causes Hypertension
• (00:16:45) - Buenos Aires Group: What Is the Kidney Secreting?
• (00:19:00) - Hypertensin vs. Angiotonin: Two Names, One Substance
• (00:22:09) - Dr. Skeggs: Angiotensin I vs II
• (00:23:30) - Sodium Chloride and the Hint of ACE
• (00:24:05) - Recap and Tease for Part Two

From mercury injections in early syphilis and heart failure patients to the discovery of carbonic anhydrase and the rise of sulfa drugs, we follow how physicians first learned to manipulate fluid balance. We also explore the development of acetazolamide and the eventual breakthrough of thiazide diuretics—revealing how observation and experimentation reshaped the treatment of heart failure and high blood pressure.

• (00:01:18) - What are diuretics?
• (00:02:28) - Mercury for congenital syphilis & surprise diuresis
• (00:08:46) - Mercury’s problems & the need for safer diuretics
• (00:10:26) - Sulfa drugs & penicillin’s first patient
• (00:12:24) - Sulfanilamide, acidosis, and the first kidney clues
• (00:15:01) - Discovery of carbonic anhydrase and its significance
• (00:17:36) - Designing better carbonic anhydrase inhibitors (Acetazolamide)
• (00:19:55) - Chlorthiazide and the thiazide era
• (00:21:26) - Wrap-up