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

Dive into the first real medications used to treat dangerously high blood pressure. From muscle poisons and anti-malarials to a plant root used for centuries, we trace how hydralazine and reserpine emerged as early antihypertensive therapies. We also explore the landmark VA Cooperative Study, which proved that lowering blood pressure could prevent strokes, heart failure, and kidney damage—and began changing modern medicine.

• (00:00:00) - Introduction: Hypertension Pharmacological Options
• (00:02:48) - Sodium Thiocyanate: The First BP-Lowering Medication
• (00:04:58) - Landmark Study: VA Cooperative
• (00:08:12) - Anti-Malarials: The Accidental Hypertension Treatement
• (00:10:29) - Pentaquine: The First Proof
• (00:13:42) - Hydralazine: An Anti-Malarial That Became a Blood Pressure Drug
• (00:15:04) - Reserpine: The Plant That Lowered Blood Pressure
• (00:19:09) - Turning Point: The Beginning of Modern Hypertension Care
• (00:22:03) - Outro: What Comes Next

Before thiazides and ACE inhibitors, clinicians relied on bleeding, low-salt diets, metabolic experiments, and even nerve-cutting surgeries to manage dangerous blood pressure. This episode explains how these early interventions—and key discoveries about volume, salt, and baroreceptors—shaped our understanding of hypertension and paved the way for pharmacologic breakthroughs.

• (00:00:00) - Introduction: Early Battles With Blood Pressure
• (00:02:08) - Bloodletting: The First “Therapy”
• (00:04:53) - Patient Story: “Mom, I Don’t Want to Die”
• (00:06:59) - Sponsor Break: Dr. Clay’s Drainage Kit
• (00:08:43) - Enter Salt: The Oldest Dietary Culprit
• (00:14:05) - Diets & The Rise of the “Rice Houses”
• (00:21:09) - Baroreceptors: The Nervous System’s Pressure Sensors
• (00:25:11) - Sympathectomies: Cutting Nerves to Cut Pressure
• (00:26:41) - Recap & What Comes Next

We trace the origins of how medicine first understood and measured blood pressure. From early fluid-pressure experiments and invasive animal studies to the invention of the modern blood-pressure cuff, we follow the slow realization that chronically elevated blood pressure is dangerous. We also explore the long-standing debate surrounding "essential hypertension" and how research—from Janeway's observations to insurance-company data and the Framingham Study—ultimately shifted medical practice toward active treatment.

• (00:00:00) - Intro: History of Blood Pressure
• (00:01:35) - What is Blood Pressure
• (00:03:53) - Normal vs High Blood Pressure
• (00:04:48) - Histories View of Hypertension
• (00:07:35) - The Origin of Blood Pressure Measurement
• (00:09:12) - Stephen Hales & Animal Experiments
• (00:12:44) - Measurement Devices
• (00:15:55) - Early Clues of Danger: Kidneys, Hearts
• (00:19:25) - What Famous Clinicians Believed
• (00:24:31) - Hypertensions Dangers Emerge
• (00:25:27) - Insurance Actuaries Enter the Scene
• (00:27:20) - The Framingham Heart Study
• (00:27:52) - Closing