The topic we’re covering this time is Angiotensin Receptor Blockers (ARBs).
In the chemical world, they are simply referred to as “ARBs.”
While they may appear to be simple blood pressure medications on the surface, they actually perform very precise roles in blood pressure control and cardiovascular protection.
Although many people still rely on old-school ACE inhibitors (ACEi) or Calcium Channel Blockers, it’s necessary to understand that, reflecting clinical data and the latest ESC/ACC guidelines, ARBs can be a better choice in specific situations.
Today, we will take a detailed look at the historical background of ARBs, the characteristics of each individual drug, and even their additional mechanisms.
Let me state upfront that I am not a doctor, and this content is not medical advice.
ARBs are prescription medications and must be used under the guidance of a physician; sourcing unverified products online is dangerous.
A sudden drop in blood pressure or misuse of medication can jeopardize your health, so caution is required.
First, let’s touch on the historical background.
Calcium Channel Blockers, which first appeared in the United States in the 1960s, had blood pressure-lowering effects but were limited by many side effects.
Aldosterone antagonists that emerged in the 1970s also showed similar limitations.
In the 1980s, with the advent of ACE inhibitors, a viable treatment option was secured, and with the development of ARBs in the 1990s, a more advantageous option for blood pressure control and long-term cardiovascular protection became available.
However, ACE inhibitors are still useful as first-line treatments in specific situations like heart failure and diabetic kidney disease, and the key point is that ARBs can be a “better choice” in cases where side effects or tolerability are issues, or for patients who have experienced side effects from ACEi.
ARBs provide blood pressure-lowering effects similar to ACE inhibitors while having significantly fewer characteristic ACEi side effects like cough or angioedema.
To understand the mechanisms related to blood pressure, one must first know about the Renin-Angiotensin System (RAS).
When blood vessels are excessively dilated, leading to low blood pressure, the kidneys secrete renin.
This renin converts angiotensinogen, produced in the liver and central nervous system, into Angiotensin I, and ACE converts this into Angiotensin II.
ACE both produces Angiotensin II and breaks down bradykinin, which contributes to vasodilation.
The key is that Angiotensin II acts on AT1 and AT2 receptors.
The AT1 receptor is the primary mediator of blood pressure elevation and side effects, while the AT2 receptor performs beneficial actions like tissue protection and neuroprotection.
AT1 receptors are present in vascular smooth muscle, adrenal glands, and adrenergic nerve synapses.
Therefore, blocking AT1 inhibits vasoconstriction and some adrenergic signaling.
This leads to decreased secretion of vasopressin and aldosterone, and while renin increases due to feedback, the blood pressure rise is blocked by ARBs or ACE inhibitors.
Furthermore, the manifestation of hypertension is influenced by polygenic genetic factors involving more than 30 intertwined SNPs.
Referring to field experience, some bodybuilding-related materials list supplements unrelated to blood pressure.
In reality, hypertension places a significant burden on the kidneys and cardiovascular system, so if using medication, blood pressure must be monitored regularly.
We recommend recording it at least 3 times a day over a weekly period; if systolic/diastolic pressure exceeds 120/80, it’s already a state requiring management, and if it’s 130/80~90 or above, continuous stress is being placed on the cardiovascular system.
Let’s examine the individual characteristics of ARBs in earnest.
Azilsartan has a very potent blood pressure-lowering effect, surpassing even the maximum doses of other ARBs, but in clinical practice, other ARBs with various additional effects are often chosen.
The most important criteria when selecting an ARB are its AT1 vs. AT2 receptor selectivity and its pharmacological properties.
Valsartan has very high AT1 selectivity of 30,000-fold and few side effects, making it suitable for patients starting ARBs for the first time.
Telmisartan has an AT1 selectivity of 3,000-fold, a 24-hour half-life, and 43% bioavailability, enabling long-term and stable blood pressure control.
Additionally, through partial PPAR-γ agonism, it improves insulin sensitivity and provides benefits like vasodilation, inflammation reduction, improvement of cardiac fibrosis, and simultaneous management of blood sugar and cardiovascular risk without weight gain.
Losartan has an AT1 selectivity of 1,000-fold, a half-life of 6-9 hours, 33% bioavailability, while also having prominent uric acid excretion promotion and kidney protection effects, and it possesses anti-inflammatory efficacy as well.
These characteristics more concretely explain the reasons for choosing ARBs other than Azilsartan and clearly present the rationale for selection based on clinical situations and patient characteristics.
Blocking the AT1 receptor brings about various changes in the heart, muscles, and brain as well.
Long-term hypertension causes left ventricular hypertrophy, but ARBs reduce heart size independently of their blood pressure-lowering effect.
They also inhibit fibrosis that occurs after muscle damage, and in the brain, while AT1 signaling increases harmful reactive oxygen species production, AT2 signaling promotes neuroprotection and BDNF production.
Therefore, by blocking AT1 with ARBs, angiotensin II binds more to AT2 receptors, yielding effects such as improved cerebral blood flow, enhanced axonal plasticity, improved learning and memory capacity, and stress reduction.
Furthermore, ARBs inhibit the NF-κB and STAT3 signaling pathways, preventing excessive microglial activation, and can reduce the risk of neurodegenerative diseases like Parkinson’s, Alzheimer’s, Huntington’s, and multiple sclerosis.
Telmisartan, due to its lipophilic nature, crosses the blood-brain barrier, and multiple mechanisms have been reported, including downregulation of AT1 mRNA expression, AMP kinase activation, mTOR inhibition leading to suppression of hepatocellular carcinoma growth, PPAR-γ-mediated inhibition of ovarian cancer cell proliferation, and induction of apoptosis in prostate cancer cells.
From a gym performance perspective, ARBs have an action that partially suppresses sympathetic nervous system overactivity.
Unlike clenbuterol or some steroids that increase instantaneous power, ARBs create a stable cardiovascular environment and contribute to long-term tissue recovery and maintaining competitiveness.
For top-tier professional bodybuilders, there might be a possibility of a slight decrease in strength, but maintaining undamaged kidney function and a stable blood pressure environment is far more important for long-term survival and performance maintenance.
Therefore, there is almost no reason to hesitate using ARBs in a state of hypertension.
References
1. StatPearls: Angiotensin II Receptor Blockers (ARB)
Comprehensively explains the basic mechanism of action, clinical efficacy, and side effects of ARBs.
Link: https://www.ncbi.nlm.nih.gov/books/NBK537027/
2. The Comparative Efficacy and Safety of the Angiotensin II Receptor Blockers: A Systematic Review
A systematic review analyzing the blood pressure-lowering effects and side effects by comparing 8 types of ARBs.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC4303500/
3. Mechanisms for the Clinical Benefits of Angiotensin II Receptor Blockers
A study covering the selective AT1 receptor blocking mechanism of ARBs and their clinical benefits.
Link: https://pubmed.ncbi.nlm.nih.gov/15882557/
4. Comparative First-Line Effectiveness and Safety of ACE Inhibitors and Angiotensin Receptor Blockers
A study comparing the effectiveness and safety of ACE inhibitors and ARBs as first-line treatments.
5. Angiotensin II receptor blockers in the management of hypertension: A real-world perspective
A review article covering the real-world effectiveness and recommendations of ARBs in hypertension management.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC9285525/
