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Department of Medicine, Sir JJ Group of Govt Hospitals & Grant Medical College, India
Submission: June 17, 2017; Published: July 19, 2017
*Corresponding author: Deepak K Jumani, Sexual Health Physician and Counselor, Department of Medicine, Sir JJ Group of Govt. Hospitals & Grant Medical College, Mumbai, India, Email: firstname.lastname@example.org
One out of three adult Indians have Hypertension, unfortunately less than 50 percent of the hypertensives get diagnosed, only 12 percent of hypertensive’s in the urban population and 9 percent of hypertensives in rural population achieve Blood pressure control . Let us now look into the worldwide statistics of hypertension and the morbidity and mortality associated with hypertension.
Hypertension is a major public health concern globally. According to estimates from the World Health Organization, approximately 40% of adults aged 25 years or more were diagnosed with hypertension in the year 2008. The number of people diagnosed with hypertension increased from 600 million in 1980 to 1 billion in 2008. The prevalence of hypertension in adults aged 25 years or more is the highest, at 46% in Africa, and the lowest at 35% in the Americas  (Figure 1).
Literature evidence shows a linear and continuous
association between blood pressure level and cardiovascular
morbidity and mortality, irrespective of age or sex. Similarly,
reduction in blood pressure levels translates into a decreased
incidence of cardiovascular and cerebrovascular complications.
As shown in the slide, hypertension is an important contributor
to the cardiovascular disease continuum. Dzau et al. first
conceived the concept of cardiovascular disease continuum in
Cardiovascular disease continuum is a sequence of
events, precipitated by cardiovascular risk, which if left
untreated, eventually leads to end-stage heart failure and
death. HTN is an important risk factor which can precipitate
this disease continuum. Other cardiovascular risk factors
include dyslipidemia, diabetes, obesity and smoking. There is
growing evidence that early intervention in managing these
cardiovascular risk factors is more crucial than treating the
disease itself . Thirty percent of Hypertensive men suffer from
Erectile Dysfunction (ED), in fact there is a growing evidence
which suggest that ED is an early sign of Hypertension. Erectile
dysfunction in men and Hypertension occur due to Endothelial
Dysfunction as endothelial dysfunction leads to contraction of
the corpora smooth muscles of the penile architecture. Today
the concept of endothelial health is that Penis is the Barometer
of Endothelial health which forms the root of every cardiovascular
pathophysiology. So an intact endothelium is a basic requirement
for a normal vascular homeostasis, which allows contractions
and relaxations of the corpora spongiosal smooth muscle, which
determines the normal blood pressure maintenance.
ED is defined as the regular inability to reach or maintain a
penile erection of sufficient quality to perform satisfactory sexual
intercourse; it has been progressively associated with many comorbities.
There are two main intracellular mechanisms for
relaxing the cavernosal VSM leading to normal erectile function:
the guanylate cyclase (GS)/cGMP and adenylate cyclase (AC)/
cAMP pathways. Both pathways results in NO release, which
is the main factor initiating erection. NO is produced by
endothelial (eNOS) or neuronal (nNOS) nitric oxide synthase
via acetylcholine or neuronal stimulation. Upon its release, NO
diffuses locally into adjacent VSMC of the corpus cavernosum
and binds to GC, which catalyzes the conversion of guanosine
trisphosphate (GTP) to cGMP. Consequently, protein kinase
G (PKG) is activated, leading to a decrease in cytosolic Ca2+ by
various mechanisms. cGMP also blocks Rho-kinase activation.
The decay in cytosolic Ca2+ concentration induces relaxation
of the VSMC in the penis, leading to dilation of arterial vessels,
increased blood flow into the corpora cavernosa, allowing
penile erection. Contributing to penile relaxation and reduction
of intracellular Ca2+, other substances activate the enzyme AC,
leading to cAMP production, which in turn activates protein
kinase A (PKA) . The erectile process is completely dependent
on relaxation and intact endothelium function, which is also true
for vascular homeostasis and normal BP maintenance. cGMP
and cAMP levels are modulated by phosphodiesterase (PDE)
enzymes, which cleave these signaling molecules to 5’GMP.
Another mechanism involved in maintenance of the erectile
process is the phosphatidylinositol 3-kinase (PI3-kinase)
pathway that activates the serine/threonine protein kinase
Akt (also known as PKB). PKB causes direct phosphorylation
of eNOS, reducing the enzyme’s Ca2+ requirements and causing increased production of NO. It has been suggested that rapid,
brief activation of nNOS initiates the erectile process, where as
PI3-kinase/Akt-dependent phosphorylation and activation of
eNOS by augmented blood flow and endothelial shear stress lead
to sustained NO production and maximal erection.
Certain neurotransmitters like Angiotensinogen II which
leads to contraction of the corpora spongiosa smooth muscle
and sodium retention are also responsible for hypertension.
Studies have shown a increase in Angiotensinogen II in the
cavernous blood of patients having erectile dysfunction. Other
neurotransmitter endothelin 1 which is also an endothelium
derived peptide also through activation of its receptors ET A
and ET B exert a vasoconstrictor effect on the corpora spongiosa
and it also has a vasoconstrictor effect on internal pudendal
artery which supplies blood to the penile vasculature. All these
neurotransmitters bring about morphological changes in the
penile vasculature by reduction of elastic fibers, increase in the
collagen of the sinusoids and thinning of the tunica albugenia.
Also seen is increase in connective tissue in the amyelinated
nerves which results in diminished blood supply to the penis.
During hypertension the endothelium produces less NO as its
production is scavenged by increase in ROS generation. Many
vascular diseases like atherosclerosis are known to begin
because of interaction between ROS and NO and ultimately lead
to diminish NO and damage to mitochondria which leads to
apoptosis and cell death.
Anti-hypertensive Therapy though there are over 100
antihypertensive agents yet hypertensions is a burning issue and
a huge economic burden.
The class of antihypertensive drugs is,
o Beta Blockers
o Calcium Channel Blockers
o Ace Inhibitors
o Angiotensinogen 2 receptor Blockers
o Centrally acting Agents
Most of the antihypertensive agents produce sexual
dysfunctions like erectile dysfunction in males except Calcium
Channel Blockers and Angiotensinogen receptor Blockers.
Diuretics reduce sodium reserves, and reduce the blood volume
and increase peripheral resistance. Beta Blockers directly
cause erectile dysfunction, Calcium Channel blockers reduce
the influx of Calcium and dilate the arteries. Ace inhibitors and
angiotensinogen receptor blockers by increasing bradykinin
levels and vasodilation.
A detailed sexual history should be obtained in patients with
new onset of hypertension before initiating drug therapy. The
sexual complaints of the patients may necessarily not be due to
medications or their side effects. The least number and lowest
dose of blood pressure medication drugs should be used to
manage hypertension. Patients who do not take medicines for
hypertension because of the side effects should be followed up
Detailed sexual history in males includes asking about
erections less than full, during coitus, early morning, during
masturbation, in all sexual and asexual situations, adequate
erections during foreplay lost before intromission, presence of
underlying medical illness and ejaculatory disturbances.
Since AngII plays an important role in the etiology of ED
during hypertension. Studies showed that treatment with ARBs
improves endothelial function in the cavernosal tissue. Studies
have shown that treatment of hypertensive patients with ARBs
resulted in improved sexual activity and erectile function.
o The phosphodiesterase type 5 inhibitors (PDE5I) are
ideal and accepted treatment for ED. PDE5I act by inhibiting
PDE5, the enzyme that catalyses the breakdown of the
second messenger cGMP.
o The PDE5I are used also for the treatment of pulmonary
hypertension (PAH). However, patients treated with nitrates
or nitrate-donors or vasodilators such as α-blockers should
not take PDE5I, otherwise, combining these drugs will result
o Treatment with β-blockers is considered to cause ED.
o However, the new generation β-blocker nebivolol may
have positive effects on erectile function. Recent studies
showed that nebivolol treatment improves endothelial
function and reverses ED in animals through the activation of the NO/cGMP pathway. Nebivolol was shown to dilate
penile arteries and treatment of hypertensive patients with
nebivolol significantly improved erectile function  (Figure
o In a Randomised double blind parallel group multicentric
clinical trial on Atpure (S Atenelol 25mg) versus
Racemic Atenelol 50mg in stage 1 & 2 Hypertension reveled
that in all the 300 patients studied at 6 centers in India, HR
and BP reduction was not significantly different. A significant
finding was that In Atenelol 50mg group, 2 patient s had
Bradycardia, 7 had brochospasms & 24 patients have loss
of libido. But in In S Atenelol 25mg none had Bradycardia
or bronchospams and no changes in Libido were seen 
o Treatment of patients with diuretics alone or with
diuretics added to their therapy was shown to worsen sexual
dysfunction. Amongst all diuretics Indepamide has shown to
have less sexual side effects in men.
o In a meta analysis of randomized, double blind, placebo
controlled trials on effect of oral L Agrinine supplementation
on Blood pressure in humans revealed that oral L Arginine
supplementations significantly lowers systolic as well as
diastolic Blood pressure. L Arginine is known to improve
endothelium dependant dilatation and reduces monocyte
adhesion to endothelial cells in young men with coronary
artery disease [8,9].
Current drugs, although effective, have poor compliance, are
expensive and short-lasting (hours or one day). Gene therapy
offers a way to produce long-lasting antihypertensive effects
(weeks, months or years). We are currently using two strategies:
antisense oligodeoxynucleotides (AS-ODN) and antisense DNA
delivered in viral vectors, to inhibit genes associated with
vasoconstrictive properties. The results of these trials in rats
have shown no sexual dysfunctions.
Erectile Dysfunction is a result of Endothelial Dysfunction.
Erectile Dysfunction usually occurs before Hypertension sets in.
Of all the antihypertensive drugs, ARB’s are the drugs which are
sex neutral and amongst the beta blockers Nebevelol, amongst
the diuretics Indepamide have less sexual dysfunctions in
males. Atpure (S Atenelol 25mg) showed no decrease in sexual
Salt restricted Diet and Exercise irrefutably are the default
treatment followed by proper evaluation prior to initiating
antihypertensive therapy and In future Gene therapy in
hypertension shall be a promising therapy.