Nebivolol: The Ultimate Anti-Hypertensive

By /u/MezDez

Background

As we know, anabolic hormones alter the renin-angiotensin-aldosterone system causing potential changes in salt balance, water retention, blood volume, then subsequently hypertension, LVH and kidney damage. Aside from this mechanism, anabolic hormones also appear to increase noradrenergic response due to their androgenic signalling.


Coupled with changes in LDL and HDL ratio, not really a pleasant environment for your heart, arteries, circulation.

  1. Standard (non selective) beta blockers causes major alterations in insulin sensitivity and lipid mobilisation. Resulting in type 2 diabetes, and therefore fatloss becoming exceedingly diminished.
  2. Angiotensin II receptor antagonist and ACE inhibitors lower plasma noradrenaline levels. Not exactly a good thing when you need this to increase for optimal CNS engagement (strength), fat loss, and energy.

I’ve looked in to all these other classes of drugs used to treat hypertension (except diuretics), and they all have side effects that are not exactly ideal. Generally, they don’t target the core issue, in relation to hormone use, this being alterations in the system I mentioned above. Instead they increase Renin and Aldosterone as a compensatory mechanism whilst masking/overriding their effects.

Here comes Nebivolol. A cardioselective beta 1 antagonist. It is also a beta 3 agonist. Amazing. It has profound nitric oxide properties as well. It doesn’t alter exercise tolerance, it actually aids in fat loss, it doesn’t alter plasma noradrenaline levels (it just blocks noradrenaline from acting on the beta 1 receptors in the heart and kidneys); Lowers renin and aldosterone; It reverses LVH; increases glucose and lipid metabolism; increases total Testosterone by 80-90%; and many more including reduction in ED… literally void of any side effects (aside from hypotension and minor other things - all dose dependant).

Studies

“In the nebivolol group, a significant decrease in blood pressures (P < 0.001) and heart rate (P < 0.01) was seen. Nebivolol therapy also suppressed plasma renin and aldosterone concentration (P < 0.02) but increased plasma atrial natriuretic peptide levels (P < 0.03)”

http://www.sciencedirect.com/science/article/pii/016752739290238X


Angiotensin II receptor antagonist increase Renin and Aldosterone, whilst Nebivolol decreases.

http://www.sciencedirect.com/science/article/pii/S193317111500618X


“Nebivolol is endowed with peripheral vasodilating properties mediated by the modulation of the endogenous production of nitric oxide. It does not significantly decrease airway conductance compared with atenolol and propranolol. Nebivolol does not compromise the left ventricular function, but it may increase stroke volume, and does not reduce heart inotropism during exertion”

http://www.sciencedirect.com/science/article/pii/S1043661898903875


“Nebivolol, through β3AR, is able to induce lipolysis and promote thermogenic and mitochondrial genes. The induction of lipolysis and the thermogenic program could explain the reduction of lipid droplets size”

http://journals.lww.com/jhypertension/Abstract/2014/02000/Nebivolol_induces,_via__3_adrenergic_receptor,.25.aspx


“nebivolol does not alter exercise capacity significantly in healthy volunteers.”

https://link.springer.com/article/10.1007/BF00051145


“Our findings in these short-term trials confirm previous reports regarding the neutral effects of nebivolol on lipid profile and carbohydrate metabolism.21,22 Recent data suggest that compared with metoprolol, nebivolol at a comparable dose improved oxidative stress and insulin sensitivity, decreased plasma soluble P-selectin, and increased adiponectin levels in hypertensive patients.”

http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7176.2009.00119.x/full


“Free fatty acid, free glycerol, plasma catecholamines, beta-endorphines and atrial natriuretic peptide (ANP) increased before and after treatment during maximal and submaximal exercise but remained unaltered by nebivolol treatment”

“nebivolol did not negatively affect lipid and carbohydrate metabolism and substrate flow.”

https://www.ncbi.nlm.nih.gov/pubmed/11607802


“Bisoprolol and nebivolol significantly increased concentration of testosterone (by 82 and 85%, respectively) and prolactin (by 77 and 83%, respectively), lowered levels of estradiol and follicle-stimulating hormone, improved vascular blood flow in penile arteries, and did not worsen sexual function.”

http://europepmc.org/abstract/med/18260876


“Nebivolol Reverses Endothelial Dysfunction in Essential Hypertension”

http://circ.ahajournals.org/content/104/5/511.short


“Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells”

https://academic.oup.com/cardiovascres/article/49/2/430/400450


“Nebivolol: A Novel Beta-Blocker with Nitric Oxide-Induced Vasodilatation”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1993984/


“Results of the present study demonstrate an inhibitory effect of nebivolol on several components of the atherosclerotic plaque which contribute to its progression. As compared to the control mice, the nebivolol-treated animals showed, along with significantly lower plaque size, a decrease in necrotic core size, collagen content, macrophage and T cell density, and activity of matrix metalloproteinases. In contrast, the drug increased the content of smooth muscle cells in the fibrous cap of the plaque.”

http://jpp.krakow.pl/journal/archive/12_13/articles/08_article.html


“In hypertensive patients with LVH, nebiviolol, combined with thiazide diuretics, significantly decreased LVMI. Moreover, Nebivolol was able to modify LV geometry from concentric to eccentric. Such effects were significantly higher in patients treated with nebivolol 5 mg/daily than in patients treated with ramipril 2.5 mg/daily. The clinical implication of these results is that the\ treatment with nebivolol/thiazides in hypertensive patients reduces the cardiovascular risk associated with LVH”

“Both nebivolol and ramipril reduced left ventricular mass and left ventricular mass index, but the effect of nebivolol was significantly higher than ramipril. Nebivolol was also able to induce a statistically significant change in the left ventricular geometry evaluated by the relative wall thickness, a marker of cardiovascular risk. “

Nebivolol reduces arterial stiffness and central blood pressure which have a pathogenetic role in promoting left ventricular hypertrophy”

http://www.europeanreview.org/wp/wp-content/uploads/1269.pdf


“Available data suggest that nebivolol has a protective effect on left ventricular function. The drug appears to reduce preload and maintain or decrease afterload. Total peripheral vascular resistance did not increase in any study of nebivolol. Heart rate and left ventricular end-diastolic pressure are decreased, whereas stroke volume is increased and cardiac output is generally maintained, notably in patients with heart failure. Nebivolol reduced left ventricular mass in hypertensive patients with left ventricular hypertrophy.”

https://link.springer.com/article/10.2165/00003495-199957040-00011


Usage

I personally use 1.25mg per day as a preventative measure in the background. However, dose can be increased depending on how high your blood pressure is.

Bioavailability is low at around ~10%. Sublingual administration have been shown to increase this by 7 fold.


Synergism

Works in synergy with diuretics as well as NO promoters like Citrulline and PDE5 inhibitors.


Note

Issues with water retention may not be resolved with any antihypertensives except diuretics. Where water retention is concerned, a thiazide-like diuretic like Chlortalidone (Chlorthalidone) can be used. Chlorthalidone also has novel mechanism that sets it apart from other diuretics. A write up will be done on Chlortalidone soon to illustrate how important this particular diuretic is to anabolic steroid users - it will literally reverse LVH and reduce left ventricular mass. Chlortalidone alone will normalise blood pressure to perfect levels for those who have hypertension due to water retention.