Blood Pressure/Hypertension not dropping

[Peptidesearch]

I don't get it. What does it matter whether you stop the synthesis of aldosterone or block it at its receptor? It seems exactly analogous to the difference between ACEIs and ARBs: You can block the synthesis of angiotensin 2, or you can block it at its receptor, and either way, you get almost exactly the same side effects and benefits. The few differences are small, and mostly about kinetics and off target action.

We already have spironolactone and eplerenone, both of which work well, with well described side effects. Is there any mechanistic reason we should expect this new synthesis inhibitor to perform better? Like, is there some reason this would cause less hyperkalemia? I can't think of one.

As far as I can tell from my limited googling, the phase 3 trial didn't directly compare baxdrostat to BP-equivalent doses of MRA drugs. And until they do, I see no reason to presume it should be better.

I hate to be too cynical, but this seems more like a drug company play to juice exclusivity out of a mechanism already well addressed by generics. No?

Great question, from what I understand, aldosterone is cardio and renal toxic so it's best to keep it's production down closer to normal levels.

Google AI summary

Excess aldosterone is cardiorenal toxic,

harming the heart and kidneys through inflammation, fibrosis, and oxidative stress, leading to issues like heart failure, left ventricular hypertrophy, chronic kidney disease, and increased cardiovascular events, even beyond its classic role in blood pressure regulation via sodium/potassium balance. It causes cardiac remodeling, mitochondrial damage, and promotes oxidative stress in both organs, making mineralocorticoid receptor antagonists (MRAs) crucial for treatment.

Renal Toxicity

Inflammation & Fibrosis : Aldosterone promotes inflammation and scarring (fibrosis) in the kidneys, damaging podocytes and glomeruli.

Glomerular Hyperfiltration : It causes kidneys to work too hard (hyperfiltration), leading to gradual decline in function.

Oxidative Stress : Generates reactive oxygen species (ROS), causing cell damage.

Cardiovascular Toxicity (Cardiotoxicity)

Cardiac Remodeling : Promotes hypertrophy (thickening) and fibrosis of heart muscle, increasing risk for heart failure and arrhythmias.

Oxidative Stress : Induces ROS production in heart cells, damaging mitochondria and reducing ATP (energy).

Vascular Damage : Contributes to arterial thickening and endothelial dysfunction.

Increased Risk : Elevates risk for heart attacks, stroke, and sudden cardiac death.

Mechanism

Mineralocorticoid Receptor (MR) : Aldosterone binds to MR, acting as a transcription factor (genomic effects) or triggering rapid signals (nongenomic effects).

Oxidative Stress : It increases NADPH oxidase activity, boosting ROS production.

Treatment & Prevention

Mineralocorticoid Receptor Antagonists (MRAs) : Drugs like spironolactone (Aldactone) and eplerenone block aldosterone's harmful effects on the heart and kidneys.

Antioxidants : Can help mitigate oxidative damage.

 

[diogenes]

Great question, from what I understand, aldosterone is cardio and renal toxic so it's best to keep it's production down closer to normal levels.

Google AI summary

Excess aldosterone is cardiorenal toxic,

harming the heart and kidneys through inflammation, fibrosis, and oxidative stress, leading to issues like heart failure, left ventricular hypertrophy , chronic kidney disease , and increased cardiovascular events, even beyond its classic role in blood pressure regulation via sodium/potassium balance. It causes cardiac remodeling, mitochondrial damage, and promotes oxidative stress in both organs, making mineralocorticoid receptor antagonists (MRAs) crucial for treatment.

Renal Toxicity

Inflammation & Fibrosis : Aldosterone promotes inflammation and scarring (fibrosis) in the kidneys, damaging podocytes and glomeruli.

Glomerular Hyperfiltration : It causes kidneys to work too hard (hyperfiltration), leading to gradual decline in function.

Oxidative Stress : Generates reactive oxygen species (ROS), causing cell damage.

Cardiovascular Toxicity (Cardiotoxicity)

Cardiac Remodeling : Promotes hypertrophy (thickening) and fibrosis of heart muscle, increasing risk for heart failure and arrhythmias.

Oxidative Stress : Induces ROS production in heart cells, damaging mitochondria and reducing ATP (energy).

Vascular Damage : Contributes to arterial thickening and endothelial dysfunction.

Increased Risk : Elevates risk for heart attacks, stroke, and sudden cardiac death.

Mechanism

Mineralocorticoid Receptor (MR) : Aldosterone binds to MR, acting as a transcription factor (genomic effects) or triggering rapid signals (nongenomic effects).

Oxidative Stress : It increases NADPH oxidase activity, boosting ROS production.

Treatment & Prevention

Mineralocorticoid Receptor Antagonists (MRAs) : Drugs like spironolactone ( Aldactone ) and eplerenone block aldosterone's harmful effects on the heart and kidneys.

Antioxidants : Can help mitigate oxidative damage.

OK, but this is an argument for using MRAs (spironolactone, eplerenone), not a reason preventing aldosterone synthesis would be more protective

 

[FRMN01]

I eat a banana everyday, partly for the fiber, but mostly for lowering my blood pressure.

Best and Worst Foods for Lowering High Blood Pressure

Nearly half of adults have high blood pressure, a.k.a. hypertension. Learn which everyday foods can reduce blood pressure and which common choices may quietly raise it.

www.aarp.org

If you eat more than one, it will also help. Years ago, when on a diet I was eathing 2-3 banannas a day. My blood pressure got really low. But I was also really young then too.

Interesting, I love bananas. Will try for a week and see if it helps