Cell Biochem Biophys
DOI 10.1007/s12013-013-9791-5
REVIEW PAPER
Non-steroidal Anti-inflammatory Drugs and Hypertension
Liuying Zheng • Xinping Du
Ó Springer Science+Business Media New York 2013
Abstract Non-steroidal anti-inflammatory drugs (NSA-
IDs) are frequently used to alleviate pain of the patients
who suffer from inflammatory conditions like rheumatoid
arthritis, osteoarthritis, and other painful conditions like
gout. This class of drugs works by blocking cyclooxgen-
ases which in turn block the prostaglandin production in
the body. Most often, NSAIDs and antihypertensive drugs
are used at the same time, and their use increases with
increasing age. Moreover, hypertension and arthritis are
common in the elderly patients requiring pharmacological
managements. An ample amount of studies put forth evi-
dence that NSAIDs reduce the efficiency of antihyperten-
sive drugs plus aggravate pre-existing hypertension or
make the individuals prone to develop high blood pressure
through renal dysfunction. This review will help doctors to
consider the effects and risk factors of concomitant pre-
scription of NSAIDs and hypertensive drugs.
Keywords Non-steroidal anti-inflammatory drugs

Hypertension
NSAIDs
High blood pressure

Prostaglandins
Antihypertensive drugs
Renal
injury
Introduction
Non-steroidal anti-inflammatory drugs (NSAIDs) are the
drugs used to ameliorate chronic pain, to reduce inflam-
L. Zheng
X. Du (&)
The Fifth Central Hospital of Tianjin, No. 41 Zhejiang Road,
Tanggu District, Tianjin 300450, China
e-mail: Xpdu2002@163.com
mation and to decrease swelling caused by different con-
ditions. NSAIDs are commonly used to treat a type of
chronic arthritis called rheumatoid arthritis (RA) [1]. These
drugs reduce the production of inflammatory substances
called prostaglandins (PGs) by blocking the enzymes
called cyclo-oxygenases (COX) [2]. Although NSAIDs are
much effective to reduce pain and inflammation, at the
same time, these drugs have been reported to cause various
adverse effects such as gastrointestinal mucosal injury [3],
peptic ulcers [4], renal complications [5, 6], edema [6], and
high blood pressure [7, 8].
Abnormally high blood pressure is one of the major
health problems that affects about one billion people all
over the world and is a significant risk factor for cardio-
vascular diseases [9, 10]. Most often, hypertension is
observed in the elderly patients especially in those who
suffer from diabetes and obesity [11]. In the same way, RA
is the disease of older people to whom NSAIDs are pre-
scribed as the first line treatment. Thus, hypertension and
RA both are the diseases of old age. In this regard, several
studies indicate that NSAIDs trigger high blood pressure in
old people [7, 8].
NSAIDs are thought to cause hypertension by several
mechanisms such as by antagonizing the anti-hypertensive
effect of the drugs or by affecting the renal function [12].
In other words, when NSAIDs and anti-hypertensive
drugs like angiotensin converting enzyme inhibitors
(ACEIs) or angiotensin receptor blockers (ARBs) are used
together, reduced antihypertensive effect is observed.
Moreover, acute renal failure and activation of renin-
angiotensin system have been reported with the use of
NSAIDs [6]. This review will offer enough evidence to
help practitioners to use NSAIDs with special caution in
those who suffer from hypertension or are at risk of
developing it.
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Literature Review
An online search on PubMed (the most reliable medical
database) was carried out using different keywords or their
combination like non-steroidal anti-inflammatory drugs or
NSAIDs and hypertension, or antihypertensive drugs or
renal injury. Mostly, full and free available articles
addressing the title of interest were studied and included in
the review. How NSAIDs affect the effects of antihyper-
tensive drugs, and renal functions to contribute to hyper-
tension is discussed below.
NSAIDs Cause Renal Injury and Salt Retention
NSAIDs are known to cause renal injury and subsequent
renal injury or dysfunction. Prostaglandins (PGs) maintain
renal haemodynamics and protect renal tubular function.
Reduced synthesis of these PGs due to NSAIDs increases
the risk of renal injury. Recently, Lapi et al. [13] studied a
cohort of 487,372 users of antihypertensive agents over
mean of 5.9 years, reporting that 2,215 patients suffered
from acute kidney injury. They demonstrated that the
patients who were undergoing triple therapy i.e., NSAIDs,
diuretics, and angiotensin converting enzyme inhibitors
(ACEIs) or angiotensin receptor blockers (ARBs) were
associated with increased risk of renal dysfunction. How-
ever, risk of renal injury was less in those who were
undergoing double therapy (combination of NSAIDs and
diuretics or ACEIs or ARBs). This is still a debatable issue
that why the renal injury was less with double therapy and
greater with triple therapy. Similarly, Moon et al. [14]
studied risk factors for NSAID-induced acute renal injury
including 328 patients with hyperuricaemia and reported
that 9.1 % of the patients developed acute renal injury. In
this way, acute renal injury leads to chronic kidney disease
(CKD) causing hypertension along with many other
complications.
Wei et al. [15] conducted a population-based longitu-
dinal analysis using GFR reporting and reported that
stopping NSAIDs treatment significantly improved the
estimated renal function. In a case report, John et al. [16]
have discussed that NSAIDs cause renal injury in the
children. Thus, increasing popularity of NSAIDs use in
children may put numerous children at risk of renal injury
and subsequent development of high blood pressure.
Therefore, there is urgent need of further studies to eval-
uate the effect of NSAIDs in children. Similarly, Kateros
et al. [17] conducted a retrospective study on 1,025
orthopedic patients following an elective or emergency
surgery and reported that NSAIDs were statistically sig-
nificantly correlated with kidney disease.
Yu et al. [18] studied the effect of NSAIDs on a mice
model and reported that dysregulated expression of the
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Cell Biochem Biophys
COX-2 dependent PGI2 biosynthesis affects the homeo-
static response of inner medulla. However, mechanism of
salt and water retention is not fully understood because of
the lack of enough research and publications on human
beings. Therefore, further studies on human beings are
required for further evaluation of relationship among
NSAIDs, renal injury, salt, and water retention leading to
high blood pressure.
NSAIDs Affect Antihypertensive Drugs
NSAIDs antagonize antihypertensive drugs and lower their
affectivity. In other words, NSAIDs are a risk factor for
those who are hypertensive or who are at risk of developing
hypertension. Therefore, studies conclude and recommend
special vigilance when NSAIDs and antihypertensive drugs
are used concomitantly. In 1991, Houston [19] evaluated
and demonstrated that NSAIDs may attenuate the effects of
antihypertensive drugs. Similarly, Polonia [20] demon-
strated that NSAIDs reduce the efficacy of certain antihy-
pertensive drugs e.g., beta-blockers, ACEIs, and ARBs;
however, calcium channel blockers (CCBs) seem not to be
affected by NSAIDs.
Aljadhey et al. [7] retrospectively studied the effect of
first prescription of NSAIDs on the cohort of 2,680 adult
hypertensive patients (1,340 in NSAIDs and 1,340 in
acetaminophen group). They reported that NSAIDs group
showed 2 mmHg increased systolic blood pressure (for
ibuprofen it was 2 mmHg) as compared to those in acet-
aminophen group. However, in contrast to the demonstra-
tion by Polonia [20], they reported similar increase in
systolic blood pressure with ACEIs and CCBs. Therefore,
the issue which antihypertensive drug is affected the most
by NSAIDs when used concomitantly is to be evaluated
with further studies.
Recently, Fournier et al. [21] studied the effect of
NSAIDs on the antihypertensive drugs by carrying out a
cohort study having 5,710 hypertensive patients. They
reported that concomitant use of NSAIDs with antihyper-
tensive drugs (especially ACEIs and ARBs) intensified the
hypertensive treatment. This study supports the demon-
stration by Polonia [20]. Hamzat and Ajala [22] have also
demonstrated that patients suffering from osteoarthritis and
hypertension at the same time should consider non-phar-
macological approaches instead of using NSAIDs as they
reduce the effects of antihypertensive drugs. Similarly,
Bavry et al. [23] studied and evaluated the effect of
NSAIDs among patients with high blood pressure and
coronary artery disease. They reported that chronic self-
reported NSAIDs use was associated with worse prognosis.
In a nutshell, NSAIDs are associated with reduction or
blunting in the efficacy of antihypertensive drugs in some
way. Some of the antihypertensive drugs may or may not
Cell Biochem Biophys
be affected; some may be affected less and the others may
be more. Therefore, in order to reach a definite conclusion
in terms of optimum control of blood pressure and to avoid
complications in the patients who use NSAIDs and anti-
hypertensive agents at the same time, further randomized
controlled trials are required. However, for the time being,
physicians and trainees in medicine should be careful about
the use of concomitant use of NSAIDs and antihyperten-
sive agents.
Conclusion
NSAIDs contribute to hypertension by damaging renal
functions or by blunting the antihypertensive effects of the
drugs. Physicians, post-graduate trainees, and other health-
care providers must bear in mind the effects of NSAIS,
while prescribing these agents to whom who have hyper-
tension or at risk of developing high blood pressure.
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