The perfect mixer for hypertension .
Andre Willers
28 Jun 2013
Synopsis :
Beetroot juice with alcohol will lower blood pressure .
Discussion :
1.There are lots of systems that increase BP . See Appendices
A , B , D .
2.ANP (Atrial natriuretic peptide )
But only one that
decreases BP . Produced mostly in the
heart .See Appendix C
3.Most of the vascular damage is not done by alcohol , but
by the hangover . See Appendix D
4.Beetroot juice is high in nitrates . See Appendix E. (Think
nitroglycerin) .
5.The BP cocktail :
2 Tots of vodka or cane
3 Tots of Beetroot juice.
Top up with ice , soda/water
Quite tasty , actually .
Watch vascular stress decrease .
Enough of these , and you won’t care , in any case .
Regards
Andre
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Appendix A
Renin-aldosterone axis in ethanol intoxication and hangover.
Linkola J, Fyhrquist F, Nieminen MM, Weber TH, Tontti K.
Abstract
The renin-aldosterone system was studied in human volunteers
during ethanol intoxication and hangover. Plasma renin activity increased more
than 100%, when 1.5 - 2.3 g ethanol per kg body weight was ingested over a
three hour period. During hangover the increase even exceeded 200%. Plasma
aldosterone concentration decreased during ethanol intoxication, but increased
greatly during hangover. It is suggested that the stimulation of the
renin-aldosterone axis during ethanol intoxication and hangover is due to dehydration
and increased activity of the sympathetic nervous system.
PMID: 1261587 [PubMed - indexed for MEDLINE]
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Appendix B
Basic Review: The Renin-Angiotensin-Aldosterone Axis
One of the coolest aspects of the
renin-angiotensin-aldosterone system (RAAS) is that it involves multiple organ
systems: the liver, lung, adrenal gland, kidney, and vasculature are all
prominently involved. It never hurts to review basic physiologic principles,
right? Listed are the three main components of the RAAS and their main
mechanisms of action.
1. Renin is a peptide hormone secreted from the
juxtaglomerular cells of the afferent arteriole in response to 3 main stimuli:
(a) renal hypoperfusion, (b) decreased distal chloride delivery to the macula
densa, and (c) increased sympathetic activity. Renin antagonists such as
aliskiren are presently being tested as antihypertensive agenst with thus far
promising results.
2. Angiotensinogen--which is synthesized and secreted from
the liver--is cleaved by renin in the systemic circulation to form angiotensin
I.
Angiotensin I is cleaved to form angiotensin II by
angiotensin converting enzyme (ACE), which is found predominantly within lung
endothelium. ACE-inhibitors, as their name implies, targets the ACE enzyme and
is one of the most potent anti-hypertensives (and GFR-preserving) therapies
available.
Angiotensin II has the following physiologic effects, which
it carries out via binding to AT1 and AT2 receptors. Drugs which block the
ability of angiotensin II to bind to its receptors ("angiotensin receptors
blockers", or ARBs) make up another highly successful and renoprotective
antihypertensive therapy. Angiotensin II binding to its receptors have the
following major effects:
a) angiotensin II acts as a systemic vasoconstrictor.
b) angiotensin II causes renal efferent arterial
vasoconstriction. Acutely, efferent vasoconstriction should increase GFR;
however, over time the increased glomerular pressure leads to glomerular damage
and, ultimately, renal injury.
c) angiotensin II increases secretion of aldosterone from
the zona glomerulosa of adrenal cortex.
3. Aldosterone: in cortical collecting duct cells,
aldosterone diffuses into the cell and interacts with the mineralocorticoid
receptor, which upon binding translocates to the nucleus and increases
expression of ENac. The end result of aldosterone action is sodium reabsorption
and potassium & hydrogen secretion. In addition to angiotensin II,
hyperkalemia can also stimulate aldosterone secretion. The drug spironolactone
interferes with aldosterone interacting with its receptors, and can be effective
in the treatment of hypertension.
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Appendix C
Atrial natriuretic peptide
From Wikipedia, the free encyclopedia
For other uses, see ANP.
Natriuretic peptide A
Atrial natriuretic peptide (ANP), atrial natriuretic factor
(ANF), atrial natriuretic hormone (ANH), Cardionatrine, Cardiodilatine (CDD) or
atriopeptin, is a powerful vasodilator, and a protein (polypeptide) hormone
secreted by heart muscle cells.[1][2][3] It is involved in the homeostatic
control of body water, sodium, potassium and fat (adipose tissue). It is
released by muscle cells in the upper chambers (atria) of the heart (atrial
myocytes) in response to high blood pressure. ANP acts to reduce the water, sodium
and adipose loads on the circulatory system, thereby reducing blood
pressure.[1] ANP has exactly the opposite function of the aldosterone secreted
by the zona glomerulosa.[4]
The ANP gene has 3 exons and 2 introns; it codes 151-amino acid
preproANP. Cleaving the 25-amino acid N-terminal results in pro-ANP. Corin, a
membrane serine protease, cleaves the final ANP, the 28-amino acid C-terminal.
ANP is produced, stored, and released mainly by cardiac
myocytes of the atria of the heart. Synthesis of ANP also takes place in the
ventricles, brain, suprarenal glands, and renal glands. It is released in
response to atrial stretch and a variety of other signals induced by
hypervolemia, exercise, or caloric restriction.[1] The hormone is constitutively
expressed in the ventricles in response to stress induced by increased
afterload (e.g. increased ventricular pressure from aortic stenosis) or injury
(e.g. myocardial infarction).
ANP is secreted in response to:
Atrial distention, stretching of the vessel walls[1]
Sympathetic stimulation of β-adrenoceptors
Raised sodium concentration (hypernatremia), though sodium
concentration is not the direct stimulus for increased ANP secretion[1]
Angiotensin-II
Endothelin, a potent vasoconstrictor
The atria become distended by high extracellular fluid and
blood volume, and atrial fibrillation. Notably, ANP secretion increases in
response to immersion of the body in water, which causes atrial stretch due to
an altered distribution of intravascular fluid. ANP secretion in response to
exercise has also been demonstrated in horses.[6]
ANP is also produced by the placenta in pregnant women. The
exact function of this remains unclear. [7]
Receptors[edit]
ANP binds to a specific set of receptors – ANP receptors.
Receptor-agonist binding causes a reduction in blood volume and therefore a
reduction in cardiac output and systemic blood pressure. Lipolysis is increased
and renal sodium reabsorption is decreased. The overall effect of ANP on the
body is to counter increases in blood pressure and volume caused by the
renin-angiotensin system.
Renal[edit]
Dilates the afferent glomerular arteriole, constricts the
efferent glomerular arteriole, and relaxes the mesangial cells. This increases
pressure in the glomerular capillaries, thus increasing the glomerular
filtration rate (GFR), resulting in greater excretion of sodium and water.
Increases blood flow through the vasa recta which will wash
the solutes (NaCl and urea) out of the medullary interstitium.[10] The lower
osmolarity of the medullary interstitium leads to less reabsorption of tubular
fluid and increased excretion.
Decreases sodium reabsorption in the distal convoluted
tubule (interaction with NCC)[11] and cortical collecting duct of the nephron
via guanosine 3',5'-cyclic monophosphate (cGMP) dependent phosphorylation of
ENaC
Inhibits renin secretion, thereby inhibiting the
renin-angiotensin-aldosterone system.
Reduces aldosterone secretion by the adrenal cortex.
Atrial natriuretic peptide (ANP) increases Na+ excretion by
decreasing the amount of Na+ reabsorbed from the inner medullary collecting
duct via a decrease in the permeability of the apical membrane of the
collecting duct epithelial cells. Less Na+ is able to enter the epithelial
cells and therefore, less Na+ is reabsorbed. ANP also increases Na+ excretion
by increasing the filtered load of Na+
Vascular[edit]
Relaxes vascular smooth muscle in arterioles and venules by:
Membrane Receptor-mediated elevation of vascular smooth
muscle cGMP
Inhibition of the effects of catecholamines
Cardiac[edit]
Inhibits maladaptive cardiac hypertrophy
Mice lacking cardiac NPRA develop increased cardiac mass and
severe fibrosis and die suddenly[12]
Re-expression of NPRA rescues the phenotype.
It may be associated with isolated atrial amyloidosis.[13]
Adipose tissue[edit]
Increases the release of free fatty acids from adipose
tissue. Plasma concentrations of glycerol and nonesterified fatty acids are
increased by i.v. infusion of ANP in humans.
Activates adipocyte plasma membrane type A guanylyl cyclase
receptors NPR-A
Increases intracellular cGMP levels that induce the
phosphorylation of a hormone-sensitive lipase and perilipin A via the
activation of a cGMP-dependent protein kinase-I (cGK-I)
Does not modulate cAMP production or PKA activity
Degradation[edit]
Regulation of the effects of ANP is achieved through gradual
degradation of the peptide by the enzyme neutral endopeptidase (NEP). Recently,
NEP inhibitors have been developed; however they have not yet been licensed.
They may be clinically useful in treating congestive heart disease.
Other natriuretic factors[edit]
In addition to the mammalian natriuretic peptides (ANP, BNP,
CNP), other natriuretic peptides with similar structure and properties have
been isolated elsewhere in the animal kingdom. Tervonen (1998) described a
salmon natriuretic peptide known as salmon cardiac peptide,[14] while
dendroaspis natriuretic peptide (DNP) can be found in the venom of the green
mamba, a species of African snake.[15]
Pharmacological modulation[edit]
Neutral endopeptidase (NEP) is the enzyme that metabolizes
natriuretic peptides. Several inhibitors of NEP are currently being developed
to treat disorders ranging from hypertension to heart failure. Most of them are
dual inhibitors. Omapatrilat (dual inhibitor of NEP and angiotensin-converting
enzyme) developed by BMS did not receive FDA approval due to angioedema safety
concerns. Other dual inhibitors of NEP with ACE/angiotensin receptor are
currently being developed by pharmaceutical companies.[16]
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Appendix D
To study the mechanisms of alcohol-induced diuresis, the
plasma concentration of immunoreactive atrial natriuretic peptide and arginine
vasopressin, serum sodium and osmolality, plasma renin activity and
aldosterone, urinary sodium and volume, free water clearance, blood pressure
and heart rate were measured in seven healthy men after oral intake of ethanol
(1.5 g kg-1 in 6 h). Serum ethanol levels increased to 27 ± 4 mmol 1-l (mean ±
SD) in 30 min and remained detectable for 14 h. Serum osmolality rose from
280±10 to 340 ± 4 mosm kg-1 in 2 hours (P < 0.01) and was 300 ± 4 at 14 h (P
< 0.01). Formation of hypotonic urine began after the alcohol intake and
resulted in a net loss of 0.9 ± 0.1 kg water in 2 h. Free water clearance
increased from -3.4 ± 1.4 to 2.8 ± 1.5ml min-l in 2 h (P < 0.01). Plasma
immunoreactive arginine vasopressin decreased from 5.7 ± 2.1 to 3.3 ± 1.3 ng
1-1 (P = 0.05) in 30 min and increased to 17 ± 25 and 12±10 ng 1-1 at 6 and 12
h, respectively (P < 0.05 for both). Plasma immunoreactive atrial
natriuretic peptide levels decreased from 17 ± 9 to the minimum of 11 ± 3 ng
1-1 in 2 h (P < 0.01) and returned to the initial levels in 6 h. Serum
sodium, plasma renin activity and plasma aldosterone increased maximally by 4
±2, 165 ± 153 and 143 ± 101 % (P < 0.01 each) during 1–6 h. No changes in
blood pressure were observed during the ingestion period, but the heart rate
rose significantly from 70 min-1 at 6 p.m. to 95 min-1 at 12 p.m.
We conclude that ethanol intake in relation to serum ethanol
levels caused in the first phase a rapid increase in osmolality which was associated
with a decrease in plasma immunoreactive arginine vasopressin. This caused
hypotonic diuresis and increased free water clearance followed by volume
contraction which evidently led to decreased plasma immunoreactive atrial
natriuretic peptide. Serum osmolality was significantly elevated during the
whole experiment and serum sodium 1–2 h after the ethanol intake. This was
associated with the return of plasma immunoreactive atrial natriuretic peptide
to initial levels after 6 h, the increase in plasma immunoreactive arginine
vasopressin levels and reduced diuresis after 2 h. Our results suggest that ANP
is not responsible for the diuresis seen after the alcohol intake.
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Appendix E
Nitric Oxide Signalling in Vascular Control and
Cardiovascular Risk
Annette Schmidt1
[1] Leibniz-Institute of Arteriosclerosis Research at the
University of Muenster, Germany
1. Introduction
Nitric oxide – a free radical molecule – has been known for
many decades, but only since its recognition as endothelium-derived relaxing
factor (EDRF) the interest in the molecule has exponentially increased (Moncada,
1991). At the present time NO is an important messenger that regulates numerous
functions and also participates in the pathogenesis of various diseases
(Lloyd-Jones & Block, 1996). NO is generated from the conversion of
arginine to citrulline in a multistep oxidation process by the NO-synthase
(NOS), a NADPH-dependent enzyme that requires Calcium-Calmodulin,
Flavinadeninedinucleotide, Flavinmononcleotide and Tetrahydro-L-biopterin as
cofactors (Förstermann et al., 1994). Three isoforms of NOS have been identified.
All isoenzymes, the neuronal NOS (nNOS), the inducible NOS (iNOS) and the
endothelial NOS (eNOS) (Liu & Huang, 2008), are homodimers with subunits of
130 – 160 kDa. As major signalling molecule of the vascular system NO is
generated by the constitutively expressed eNOS.
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